Chapter 15 : Intravital Imaging of Myeloid Cells: Inflammatory Migration and Resident Patrolling

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

Intravital Imaging of Myeloid Cells: Inflammatory Migration and Resident Patrolling, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555819194/9781555819187_Chap15-1.gif /docserver/preview/fulltext/10.1128/9781555819194/9781555819187_Chap15-2.gif


The first documented experiments using intravital microscopy were performed in the 19th century, in which very thin translucent tissues were used so that light could penetrate through the tissue and leukocyte trafficking could be observed ( ). Neither human tissues nor solid organs in animal models could be used at the time. As such, tissues like the rodent mesentery, cremaster muscle, and ear and the bat wing were the preparations of choice for the next century. This type of imaging unveiled the very dynamic interaction of immune cells with vessel walls. The experimentalists tried to keep the conditions as close to the natural environment as was feasible. The bat wing and ear vasculatures required no surgery, making them likely the least perturbed approach. The mesentery and cremaster, which required only minor surgery, likely did induce a nonphysiologic baseline of leukocyte-vessel wall interactions. However, this came with the benefit of being able to examine cellular functions and behaviors under shear forces associated with blood flow as well as the surrounding architecture of capillaries and venules that was impossible to replicate . Indeed, as diligent as experimentalists were, settings could not completely replicate the behavior of immune cells as they interacted with each other, red blood cells and platelets in capillaries and postcapillary venules surrounded by pericytes and with macrophages, mast cells, and the myriad of other resident immune and parenchymal cells that constitute a living organ. Moreover, interorgan and neural communications were also not possible . However, it is always critical to remember that rodents, bats, and fish are not humans, and so all interpretations must be made with this in mind. It is also worth mentioning that many of the discoveries were made hand in hand with key experiments that allowed simplification of the complex model to elucidate cellular and molecular events.

Citation: Deniset J, Kubes P. 2017. Intravital Imaging of Myeloid Cells: Inflammatory Migration and Resident Patrolling, p 273-293. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0042-2016
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

Classical leukocyte recruitment cascade. Depicted are the sequential steps of leukocyte recruitment from the vasculature into the tissue. Selectins and their ligands mediate initial tethering and rolling along the vascular wall. Engagement of intermediate chemokine receptors with their ligands lining the endothelium stimulates activation of integrins on the leukocyte cell surface, enabling their interaction with their respective receptors to facilitate arrest, adhesion, and subsequent transmigration by paracellular or transcellular routes. Chemotactic gradients of intermediate and end-target chemokines guide leukocytes to sites of transmigration and promote directed migration to the site of injury or infection within the tissue.

Citation: Deniset J, Kubes P. 2017. Intravital Imaging of Myeloid Cells: Inflammatory Migration and Resident Patrolling, p 273-293. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0042-2016
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

KC capture of circulating bacteria . Time-lapse spinning-disk confocal microscopy images of (-GFP; green) catching by liver KCs (F4/80; red) in wild-type (WT) (top) or CRIg (bottom) animals. White arrows, KC-bound bacteria. Bars, 50 μm.

Citation: Deniset J, Kubes P. 2017. Intravital Imaging of Myeloid Cells: Inflammatory Migration and Resident Patrolling, p 273-293. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0042-2016
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Wagner R . 1839. Erlauterungstaflen zur Physiologie und Entwicklungsgeschichte. Leopold Voss, Leipzig, Germany.
2. Ley K,, Laudanna C,, Cybulsky MI,, Nourshargh S . 2007. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7 : 678689.
3. Petri B,, Phillipson M,, Kubes P . 2008. The physiology of leukocyte recruitment: an in vivo perspective. J Immunol 180 : 64396446.
4. Ntziachristos V . 2010. Going deeper than microscopy: the optical imaging frontier in biology. Nat Methods 7 : 603614.
5. Pittet MJ,, Weissleder R . 2011. Intravital imaging. Cell 147 : 983991.
6. Lee WY,, Moriarty TJ,, Wong CH,, Zhou H,, Strieter RM,, van Rooijen N,, Chaconas G,, Kubes P . 2010. An intravascular immune response to Borrelia burgdorferi involves Kupffer cells and iNKT cells. Nat Immunol 11 : 295302.
7. McDonald B,, Pittman K,, Menezes GB,, Hirota SA,, Slaba I,, Waterhouse CC,, Beck PL,, Muruve DA,, Kubes P . 2010. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science 330 : 362366.
8. Wong CH,, Jenne CN,, Lee WY,, Léger C,, Kubes P . 2011. Functional innervation of hepatic iNKT cells is immunosuppressive following stroke. Science 334 : 101105.
9. Helmchen F,, Denk W . 2005. Deep tissue two-photon microscopy. Nat Methods 2 : 932940.
10. Ishii T,, Ishii M . 2011. Intravital two-photon imaging: a versatile tool for dissecting the immune system. Ann Rheum Dis 70(Suppl 1): i113i115.
11. Chodaczek G,, Papanna V,, Zal MA,, Zal T . 2012. Body-barrier surveillance by epidermal γδ TCRs. Nat Immunol 13 : 272282.
12. Roth TL,, Nayak D,, Atanasijevic T,, Koretsky AP,, Latour LL,, McGavern DB . 2014. Transcranial amelioration of inflammation and cell death after brain injury. Nature 505 : 223228.
13. Shaked I,, Hanna RN,, Shaked H,, Chodaczek G,, Nowyhed HN,, Tweet G,, Tacke R,, Basat AB,, Mikulski Z,, Togher S,, Miller J,, Blatchley A,, Salek-Ardakani S,, Darvas M,, Kaikkonen MU,, Thomas GD,, Lai-Wing-Sun S,, Rezk A,, Bar-Or A,, Glass CK,, Bandukwala H,, Hedrick CC . 2015. Transcription factor Nr4a1 couples sympathetic and inflammatory cues in CNS-recruited macrophages to limit neuroinflammation. Nat Immunol 16 : 12281234.
14. Coppieters K,, Amirian N,, von Herrath M . 2012. Intravital imaging of CTLs killing islet cells in diabetic mice. J Clin Invest 122 : 119131.
15. Swirski FK,, Nahrendorf M,, Etzrodt M,, Wildgruber M,, Cortez-Retamozo V,, Panizzi P,, Figueiredo JL,, Kohler RH,, Chudnovskiy A,, Waterman P,, Aikawa E,, Mempel TR,, Libby P,, Weissleder R,, Pittet MJ . 2009. Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325 : 612616.
16. Harding MG,, Zhang K,, Conly J,, Kubes P . 2014. Neutrophil crawling in capillaries; a novel immune response to Staphylococcus aureus . PLoS Pathog 10 : e1004379. doi:10.1371/journal.ppat.1004379.
17. Kreisel D,, Nava RG,, Li W,, Zinselmeyer BH,, Wang B,, Lai J,, Pless R,, Gelman AE,, Krupnick AS,, Miller MJ . 2010. In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation. Proc Natl Acad Sci U S A 107 : 1807318078.
18. Nimmerjahn A,, Kirchhoff F,, Helmchen F . 2005. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308 : 13141318.
19. Chèvre R,, González-Granado JM,, Megens RT,, Sreeramkumar V,, Silvestre-Roig C,, Molina-Sánchez P,, Weber C,, Soehnlein O,, Hidalgo A,, Andrés V . 2014. High-resolution imaging of intravascular atherogenic inflammation in live mice. Circ Res 114 : 770779.
20. Jung K,, Kim P,, Leuschner F,, Gorbatov R,, Kim JK,, Ueno T,, Nahrendorf M,, Yun SH . 2013. Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts. Circ Res 112 : 891899.
21. Looney MR,, Thornton EE,, Sen D,, Lamm WJ,, Glenny RW,, Krummel MF . 2011. Stabilized imaging of immune surveillance in the mouse lung. Nat Methods 8 : 9196.
22. Thanabalasuriar A,, Neupane AS,, Wang J,, Krummel MF,, Kubes P . 2016. iNKT cell emigration out of the lung vasculature requires neutrophils and monocyte-derived dendritic cells in inflammation. Cell Rep 16 : 32603272.
23. Aguirre AD,, Vinegoni C,, Sebas M,, Weissleder R . 2014. Intravital imaging of cardiac function at the single-cell level. Proc Natl Acad Sci U S A 111 : 1125711262.
24. McArdle S,, Chodaczek G,, Ray N,, Ley K . 2015. Intravital live cell triggered imaging system reveals monocyte patrolling and macrophage migration in atherosclerotic arteries. J Biomed Opt 20 : 26005. doi:10.1117/1.JBO.20.2.026005.
25. Heo C,, Park H,, Kim YT,, Baeg E,, Kim YH,, Kim SG,, Suh M . 2016. A soft, transparent, freely accessible cranial window for chronic imaging and electrophysiology. Sci Rep 6 : 27818. doi:10.1038/srep27818.
26. Ritsma L,, Steller EJ,, Ellenbroek SI,, Kranenburg O,, Borel Rinkes IH,, van Rheenen J . 2013. Surgical implantation of an abdominal imaging window for intravital microscopy. Nat Protoc 8 : 583594.
27. Kansas GS . 1996. Selectins and their ligands: current concepts and controversies. Blood 88 : 32593287.
28. Zarbock A,, Ley K,, McEver RP,, Hidalgo A . 2011. Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow. Blood 118 : 67436751.
29. Ala A,, Dhillon AP,, Hodgson HJ . 2003. Role of cell adhesion molecules in leukocyte recruitment in the liver and gut. Int J Exp Pathol 84 : 116.
30. Patel KD,, Cuvelier SL,, Wiehler S . 2002. Selectins: critical mediators of leukocyte recruitment. Semin Immunol 14 : 7381.
31. Lorant DE,, Patel KD,, McIntyre TM,, McEver RP,, Prescott SM,, Zimmerman GA . 1991. Coexpression of GMP-140 and PAF by endothelium stimulated by histamine or thrombin: a juxtacrine system for adhesion and activation of neutrophils. J Cell Biol 115 : 223234.
32. Chung KF . 1992. Platelet-activating factor in inflammation and pulmonary disorders. Clin Sci (Lond) 83 : 127138.
33. Theoharides TC,, Alysandratos KD,, Angelidou A,, Delivanis DA,, Sismanopoulos N,, Zhang B,, Asadi S,, Vasiadi M,, Weng Z,, Miniati A,, Kalogeromitros D . 2012. Mast cells and inflammation. Biochim Biophys Acta 1822 : 2133.
34. Muller WA . 2013. Getting leukocytes to the site of inflammation. Vet Pathol 50 : 722.
35. Massena S,, Christoffersson G,, Hjertström E,, Zcharia E,, Vlodavsky I,, Ausmees N,, Rolny C,, Li JP,, Phillipson M . 2010. A chemotactic gradient sequestered on endothelial heparan sulfate induces directional intraluminal crawling of neutrophils. Blood 116 : 19241931.
36. Williams MR,, Azcutia V,, Newton G,, Alcaide P,, Luscinskas FW . 2011. Emerging mechanisms of neutrophil recruitment across endothelium. Trends Immunol 32 : 461469.
37. Charmoy M,, Brunner-Agten S,, Aebischer D,, Auderset F,, Launois P,, Milon G,, Proudfoot AE,, Tacchini-Cottier F . 2010. Neutrophil-derived CCL3 is essential for the rapid recruitment of dendritic cells to the site of Leishmania major inoculation in resistant mice. PLoS Pathog 6 : e1000755. doi:10.1371/journal.ppat.1000755.
38. Döring Y,, Drechsler M,, Wantha S,, Kemmerich K,, Lievens D,, Vijayan S,, Gallo RL,, Weber C,, Soehnlein O . 2012. Lack of neutrophil-derived CRAMP reduces atherosclerosis in mice. Circ Res 110 : 10521056.
39. Kolaczkowska E,, Kubes P . 2013. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol 13 : 159175.
40. Phillipson M,, Heit B,, Colarusso P,, Liu L,, Ballantyne CM,, Kubes P . 2006. Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade. J Exp Med 203 : 25692575.
41. Randolph GJ,, Furie MB . 1995. A soluble gradient of endogenous monocyte chemoattractant protein-1 promotes the transendothelial migration of monocytes in vitro. J Immunol 155 : 36103618.
42. Colotta F,, Borré A,, Wang JM,, Tattanelli M,, Maddalena F,, Polentarutti N,, Peri G,, Mantovani A . 1992. Expression of a monocyte chemotactic cytokine by human mononuclear phagocytes. J Immunol 148 : 760765.
43. Kasahara T,, Mukaida N,, Yamashita K,, Yagisawa H,, Akahoshi T,, Matsushima K . 1991. IL-1 and TNF-α induction of IL-8 and monocyte chemotactic and activating factor (MCAF) mRNA expression in a human astrocytoma cell line. Immunology 74 : 6067.
44. Sica A,, Wang JM,, Colotta F,, Dejana E,, Mantovani A,, Oppenheim JJ,, Larsen CG,, Zachariae CO,, Matsushima K . 1990. Monocyte chemotactic and activating factor gene expression induced in endothelial cells by IL-1 and tumor necrosis factor. J Immunol 144 : 30343038.
45. Strieter RM,, Kunkel SL,, Showell HJ,, Remick DG,, Phan SH,, Ward PA,, Marks RM . 1989. Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-α, LPS, and IL-1β. Science 243 : 14671469.
46. Strieter RM,, Phan SH,, Showell HJ,, Remick DG,, Lynch JP,, Genord M,, Raiford C,, Eskandari M,, Marks RM,, Kunkel SL . 1989. Monokine-induced neutrophil chemotactic factor gene expression in human fibroblasts. J Biol Chem 264 : 1062110626.
47. Wang JM,, Sica A,, Peri G,, Walter S,, Padura IM,, Libby P,, Ceska M,, Lindley I,, Colotta F,, Mantovani A . 1991. Expression of monocyte chemotactic protein and interleukin-8 by cytokine-activated human vascular smooth muscle cells. Arterioscler Thromb 11 : 11661174.
48. Dinarello CA . 1992. The biology of interleukin-1. Chem Immunol 51 : 132.
49. Vassalli P . 1992. The pathophysiology of tumor necrosis factors. Annu Rev Immunol 10 : 411452.
50. Cuvelier SL,, Patel KD . 2001. Shear-dependent eosinophil transmigration on interleukin 4-stimulated endothelial cells: a role for endothelium-associated eotaxin-3. J Exp Med 194 : 16991709.
51. Hillyer P,, Male D . 2005. Expression of chemokines on the surface of different human endothelia. Immunol Cell Biol 83 : 375382.
52. Heit B,, Robbins SM,, Downey CM,, Guan Z,, Colarusso P,, Miller BJ,, Jirik FR,, Kubes P . 2008. PTEN functions to ‘prioritize’ chemotactic cues and prevent ‘distraction’ in migrating neutrophils. Nat Immunol 9 : 743752.
53. Heit B,, Tavener S,, Raharjo E,, Kubes P . 2002. An intracellular signaling hierarchy determines direction of migration in opposing chemotactic gradients. J Cell Biol 159 : 91102.
54. Chou RC,, Kim ND,, Sadik CD,, Seung E,, Lan Y,, Byrne MH,, Haribabu B,, Iwakura Y,, Luster AD . 2010. Lipid-cytokine-chemokine cascade drives neutrophil recruitment in a murine model of inflammatory arthritis. Immunity 33 : 266278.
55. Kim ND,, Chou RC,, Seung E,, Tager AM,, Luster AD . 2006. A unique requirement for the leukotriene B4 receptor BLT1 for neutrophil recruitment in inflammatory arthritis. J Exp Med 203 : 829835.
56. Andréasson E,, Önnheim K,, Forsman H . 2013. The subcellular localization of the receptor for platelet-activating factor in neutrophils affects signaling and activation characteristics. Clin Dev Immunol 2013 : 456407.
57. Fu H,, Bylund J,, Karlsson A,, Pellmé S,, Dahlgren C . 2004. The mechanism for activation of the neutrophil NADPH-oxidase by the peptides formyl-Met-Leu-Phe and Trp-Lys-Tyr-Met-Val-Met differs from that for interleukin-8. Immunology 112 : 201210.
58. Nourshargh S,, Alon R . 2014. Leukocyte migration into inflamed tissues. Immunity 41 : 694707.
59. Petri B,, Bixel MG . 2006. Molecular events during leukocyte diapedesis. FEBS J 273 : 43994407.
60. Feng D,, Nagy JA,, Pyne K,, Dvorak HF,, Dvorak AM . 1998. Neutrophils emigrate from venules by a transendothelial cell pathway in response to FMLP. J Exp Med 187 : 903915.
61. Burns AR,, Bowden RA,, MacDonell SD,, Walker DC,, Odebunmi TO,, Donnachie EM,, Simon SI,, Entman ML,, Smith CW . 2000. Analysis of tight junctions during neutrophil transendothelial migration. J Cell Sci 113 : 4557.
62. Wang S,, Voisin MB,, Larbi KY,, Dangerfield J,, Scheiermann C,, Tran M,, Maxwell PH,, Sorokin L,, Nourshargh S . 2006. Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils. J Exp Med 203 : 15191532.
63. Carman CV,, Springer TA . 2004. A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them. J Cell Biol 167 : 377388.
64. Nieminen M,, Henttinen T,, Merinen M,, Marttila-Ichihara F,, Eriksson JE,, Jalkanen S . 2006. Vimentin function in lymphocyte adhesion and transcellular migration. Nat Cell Biol 8 : 156162.
65. Cara DC,, Kaur J,, Forster M,, McCafferty DM,, Kubes P . 2001. Role of p38 mitogen-activated protein kinase in chemokine-induced emigration and chemotaxis in vivo. J Immunol 167 : 65526558.
66. Hickey MJ,, Forster M,, Mitchell D,, Kaur J,, De Caigny C,, Kubes P . 2000. L-selectin facilitates emigration and extravascular locomotion of leukocytes during acute inflammatory responses in vivo. J Immunol 165 : 71647170.
67. Johnston B,, Burns AR,, Suematsu M,, Issekutz TB,, Woodman RC,, Kubes P . 1999. Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1. J Clin Invest 103 : 12691276.
68. Johnston B,, Burns AR,, Suematsu M,, Watanabe K,, Issekutz TB,, Kubes P . 2000. Increased sensitivity to the C-X-C chemokine CINC/gro in a model of chronic inflammation. Microcirculation 7 : 109118.
69. Johnston B,, Chee A,, Issekutz TB,, Ugarova T,, Fox-Robichaud A,, Hickey MJ,, Kubes P . 2000. α4 Integrin-dependent leukocyte recruitment does not require VCAM-1 in a chronic model of inflammation. J Immunol 164 : 33373344.
70. Liu L,, Cara DC,, Kaur J,, Raharjo E,, Mullaly SC,, Jongstra-Bilen J,, Jongstra J,, Kubes P . 2005. LSP1 is an endothelial gatekeeper of leukocyte transendothelial migration. J Exp Med 201 : 409418.
71. Doerschuk CM . 2001. Mechanisms of leukocyte sequestration in inflamed lungs. Microcirculation 8 : 7188.
72. Li W,, Nava RG,, Bribriesco AC,, Zinselmeyer BH,, Spahn JH,, Gelman AE,, Krupnick AS,, Miller MJ,, Kreisel D . 2012. Intravital 2-photon imaging of leukocyte trafficking in beating heart. J Clin Invest 122 : 24992508.
73. McDonald B,, McAvoy EF,, Lam F,, Gill V,, de la Motte C,, Savani RC,, Kubes P . 2008. Interaction of CD44 and hyaluronan is the dominant mechanism for neutrophil sequestration in inflamed liver sinusoids. J Exp Med 205 : 915927.
74. Singbartl K,, Forlow SB,, Ley K . 2001. Platelet, but not endothelial, P-selectin is critical for neutrophil-mediated acute postischemic renal failure. FASEB J 15 : 23372344.
75. Wang Q,, Teder P,, Judd NP,, Noble PW,, Doerschuk CM . 2002. CD44 deficiency leads to enhanced neutrophil migration and lung injury in Escherichia coli pneumonia in mice. Am J Pathol 161 : 22192228.
76. Wong J,, Johnston B,, Lee SS,, Bullard DC,, Smith CW,, Beaudet AL,, Kubes P . 1997. A minimal role for selectins in the recruitment of leukocytes into the inflamed liver microvasculature. J Clin Invest 99 : 27822790.
77. Block H,, Herter JM,, Rossaint J,, Stadtmann A,, Kliche S,, Lowell CA,, Zarbock A . 2012. Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury. J Exp Med 209 : 407421.
78. Megens RT,, Kemmerich K,, Pyta J,, Weber C,, Soehnlein O . 2011. Intravital imaging of phagocyte recruitment. Thromb Haemost 105 : 802810.
79. Phillipson M,, Heit B,, Parsons SA,, Petri B,, Mullaly SC,, Colarusso P,, Gower RM,, Neely G,, Simon SI,, Kubes P . 2009. Vav1 is essential for mechanotactic crawling and migration of neutrophils out of the inflamed microvasculature. J Immunol 182 : 68706878.
80. Menezes GB,, Lee WY,, Zhou H,, Waterhouse CC,, Cara DC,, Kubes P . 2009. Selective down-regulation of neutrophil Mac-1 in endotoxemic hepatic microcirculation via IL-10. J Immunol 183 : 75577568.
81. Nagao T,, Matsumura M,, Mabuchi A,, Ishida-Okawara A,, Koshio O,, Nakayama T,, Minamitani H,, Suzuki K . 2007. Up-regulation of adhesion molecule expression in glomerular endothelial cells by anti-myeloperoxidase antibody. Nephrol Dial Transplant 22 : 7787.
82. Ogawa T,, Yorioka N,, Ito T,, Ogata S,, Kumagai J,, Kawanishi H,, Yamakido M . 1997. Precise ultrastructural localization of endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in patients with IgA nephropathy. Nephron 75 : 5464.
83. Kuligowski MP,, Kitching AR,, Hickey MJ . 2006. Leukocyte recruitment to the inflamed glomerulus: a critical role for platelet-derived P-selectin in the absence of rolling. J Immunol 176 : 69916999.
84. Carvalho-Tavares J,, Hickey MJ,, Hutchison J,, Michaud J,, Sutcliffe IT,, Kubes P . 2000. A role for platelets and endothelial selectins in tumor necrosis factor-α-induced leukocyte recruitment in the brain microvasculature. Circ Res 87 : 11411148.
85. Ishikawa M,, Cooper D,, Russell J,, Salter JW,, Zhang JH,, Nanda A,, Granger DN . 2003. Molecular determinants of the prothrombogenic and inflammatory phenotype assumed by the postischemic cerebral microcirculation. Stroke 34 : 17771782.
86. Grady MS,, Cody RF Jr,, Maris DO,, McCall TD,, Seckin H,, Sharar SR,, Winn HR . 1999. P-selectin blockade following fluid-percussion injury: behavioral and immunochemical sequelae. J Neurotrauma 16 : 1325.
87. Suzuki H,, Hayashi T,, Tojo SJ,, Kitagawa H,, Kimura K,, Mizugaki M,, Itoyama Y,, Abe K . 1999. Anti-P-selectin antibody attenuates rat brain ischemic injury. Neurosci Lett 265 : 163166.
88. Kuijper PH,, Gallardo Tores HI,, Lammers JW,, Sixma JJ,, Koenderman L,, Zwaginga JJ . 1998. Platelet associated fibrinogen and ICAM-2 induce firm adhesion of neutrophils under flow conditions. Thromb Haemost 80 : 443448.
89. von Hundelshausen P,, Petersen F,, Brandt E . 2007. Platelet-derived chemokines in vascular biology. Thromb Haemost 97 : 704713.
90. Weber C,, Springer TA . 1997. Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to αIIbβ3 and stimulated by platelet-activating factor. J Clin Invest 100 : 20852093.
91. Hammond MD,, Taylor RA,, Mullen MT,, Ai Y,, Aguila HL,, Mack M,, Kasner SE,, McCullough LD,, Sansing LH . 2014. CCR2+Ly6Chi inflammatory monocyte recruitment exacerbates acute disability following intracerebral hemorrhage. J Neurosci 34 : 39013909.
92. Morganti JM,, Jopson TD,, Liu S,, Riparip LK,, Guandique CK,, Gupta N,, Ferguson AR,, Rosi S . 2015. CCR2 antagonism alters brain macrophage polarization and ameliorates cognitive dysfunction induced by traumatic brain injury. J Neurosci 35 : 748760.
93. Buckley CD,, Gilroy DW,, Serhan CN,, Stockinger B,, Tak PP . 2013. The resolution of inflammation. Nat Rev Immunol 13 : 5966.
94. Hampton HR,, Bailey J,, Tomura M,, Brink R,, Chtanova T . 2015. Microbe-dependent lymphatic migration of neutrophils modulates lymphocyte proliferation in lymph nodes. Nat Commun 6 : 7139. doi:10.1038/ncomms8139.
95. Hall C,, Flores MV,, Chien A,, Davidson A,, Crosier K,, Crosier P . 2009. Transgenic zebrafish reporter lines reveal conserved Toll-like receptor signaling potential in embryonic myeloid leukocytes and adult immune cell lineages. J Leukoc Biol 85 : 751765.
96. Mathias JR,, Perrin BJ,, Liu TX,, Kanki J,, Look AT,, Huttenlocher A . 2006. Resolution of inflammation by retrograde chemotaxis of neutrophils in transgenic zebrafish. J Leukoc Biol 80 : 12811288.
97. Yoo SK,, Huttenlocher A . 2011. Spatiotemporal photolabeling of neutrophil trafficking during inflammation in live zebrafish. J Leukoc Biol 89 : 661667.
98. Woodfin A,, Voisin MB,, Beyrau M,, Colom B,, Caille D,, Diapouli FM,, Nash GB,, Chavakis T,, Albelda SM,, Rainger GE,, Meda P,, Imhof BA,, Nourshargh S . 2011. The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo . Nat Immunol 12 : 761769.
99. Colom B,, Bodkin JV,, Beyrau M,, Woodfin A,, Ody C,, Rourke C,, Chavakis T,, Brohi K,, Imhof BA,, Nourshargh S . 2015. Leukotriene B4-neutrophil elastase axis drives neutrophil reverse transendothelial cell migration in vivo. Immunity 42 : 10751086.
100. Buckley CD,, Ross EA,, McGettrick HM,, Osborne CE,, Haworth O,, Schmutz C,, Stone PC,, Salmon M,, Matharu NM,, Vohra RK,, Nash GB,, Rainger GE . 2006. Identification of a phenotypically and functionally distinct population of long-lived neutrophils in a model of reverse endothelial migration. J Leukoc Biol 79 : 303311.
101. Auffray C,, Fogg D,, Garfa M,, Elain G,, Join-Lambert O,, Kayal S,, Sarnacki S,, Cumano A,, Lauvau G,, Geissmann F . 2007. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 317 : 666670.
102. Bellavance MA,, Gosselin D,, Yong VW,, Stys PK,, Rivest S . 2015. Patrolling monocytes play a critical role in CX3CR1-mediated neuroprotection during excitotoxicity. Brain Struct Funct 220 : 17591776.
103. Carlin LM,, Stamatiades EG,, Auffray C,, Hanna RN,, Glover L,, Vizcay-Barrena G,, Hedrick CC,, Cook HT,, Diebold S,, Geissmann F . 2013. Nr4a1-dependent Ly6Clow monocytes monitor endothelial cells and orchestrate their disposal. Cell 153 : 362375.
104. Boring L,, Gosling J,, Chensue SW,, Kunkel SL,, Farese RV Jr,, Broxmeyer HE,, Charo IF . 1997. Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice. J Clin Invest 100 : 25522561.
105. Peters W,, Scott HM,, Chambers HF,, Flynn JL,, Charo IF,, Ernst JD . 2001. Chemokine receptor 2 serves an early and essential role in resistance to Mycobacterium tuberculosis . Proc Natl Acad Sci U S A 98 : 79587963.
106. Boring L,, Gosling J,, Cleary M,, Charo IF . 1998. Decreased lesion formation in CCR2–/– mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 394 : 894897.
107. Izikson L,, Klein RS,, Charo IF,, Weiner HL,, Luster AD . 2000. Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2. J Exp Med 192 : 10751080.
108. Serbina NV,, Pamer EG . 2006. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol 7 : 311317.
109. Tsou CL,, Peters W,, Si Y,, Slaymaker S,, Aslanian AM,, Weisberg SP,, Mack M,, Charo IF . 2007. Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites. J Clin Invest 117 : 902909.
110. Nahrendorf M,, Swirski FK,, Aikawa E,, Stangenberg L,, Wurdinger T,, Figueiredo JL,, Libby P,, Weissleder R,, Pittet MJ . 2007. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 204 : 30373047.
111. Hilgendorf I,, Gerhardt LM,, Tan TC,, Winter C,, Holderried TA,, Chousterman BG,, Iwamoto Y,, Liao R,, Zirlik A,, Scherer-Crosbie M,, Hedrick CC,, Libby P,, Nahrendorf M,, Weissleder R,, Swirski FK . 2014. Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium. Circ Res 114 : 16111622.
112. Sunderkötter C,, Nikolic T,, Dillon MJ,, Van Rooijen N,, Stehling M,, Drevets DA,, Leenen PJ . 2004. Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response. J Immunol 172 : 44104417.
113. Arnold L,, Henry A,, Poron F,, Baba-Amer Y,, van Rooijen N,, Plonquet A,, Gherardi RK,, Chazaud B . 2007. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J Exp Med 204 : 10571069.
114. Crane MJ,, Daley JM,, van Houtte O,, Brancato SK,, Henry WL Jr,, Albina JE . 2014. The monocyte to macrophage transition in the murine sterile wound. PLoS One 9 : e86660. doi:10.1371/journal.pone.0086660.
115. Dal-Secco D,, Wang J,, Zeng Z,, Kolaczkowska E,, Wong CH,, Petri B,, Ransohoff RM,, Charo IF,, Jenne CN,, Kubes P . 2015. A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury. J Exp Med 212 : 447456.
116. Wang J,, Kubes P . 2016. A reservoir of mature cavity macrophages that can rapidly invade visceral organs to affect tissue repair. Cell 165 : 668678.
117. Delano MJ,, Kelly-Scumpia KM,, Thayer TC,, Winfield RD,, Scumpia PO,, Cuenca AG,, Harrington PB,, O’Malley KA,, Warner E,, Gabrilovich S,, Mathews CE,, Laface D,, Heyworth PG,, Ramphal R,, Strieter RM,, Moldawer LL,, Efron PA . 2011. Neutrophil mobilization from the bone marrow during polymicrobial sepsis is dependent on CXCL12 signaling. J Immunol 187 : 911918.
118. Eash KJ,, Greenbaum AM,, Gopalan PK,, Link DC . 2010. CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow. J Clin Invest 120 : 24232431.
119. Eash KJ,, Means JM,, White DW,, Link DC . 2009. CXCR4 is a key regulator of neutrophil release from the bone marrow under basal and stress granulopoiesis conditions. Blood 113 : 47114719.
120. Martin C,, Burdon PC,, Bridger G,, Gutierrez-Ramos JC,, Williams TJ,, Rankin SM . 2003. Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence. Immunity 19 : 583593.
121. Devi S,, Wang Y,, Chew WK,, Lima R,, A-González N,, Mattar CN,, Chong SZ,, Schlitzer A,, Bakocevic N,, Chew S,, Keeble JL,, Goh CC,, Li JL,, Evrard M,, Malleret B,, Larbi A,, Renia L,, Haniffa M,, Tan SM,, Chan JK,, Balabanian K,, Nagasawa T,, Bachelerie F,, Hidalgo A,, Ginhoux F,, Kubes P,, Ng LG . 2013. Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow. J Exp Med 210 : 23212336.
122. Doerschuk CM,, Beyers N,, Coxson HO,, Wiggs B,, Hogg JC . 1993. Comparison of neutrophil and capillary diameters and their relation to neutrophil sequestration in the lung. J Appl Physiol 1985 74 : 30403045.
123. Martin BA,, Wiggs BR,, Lee S,, Hogg JC . 1987. Regional differences in neutrophil margination in dog lungs. J Appl Physiol 1985 63 : 12531261.
124. Hogg JC,, Doerschuk CM . 1995. Leukocyte traffic in the lung. Annu Rev Physiol 57 : 97114.
125. Kuebler WM,, Goetz AE . 2002. The marginated pool. Eur Surg Res 34 : 92100.
126. Kuebler WM,, Kuhnle GE,, Goetz AE . 1999. Leukocyte margination in alveolar capillaries: interrelationship with functional capillary geometry and microhemodynamics. J Vasc Res 36 : 282288.
127. Kuebler WM,, Kuhnle GE,, Groh J,, Goetz AE . 1994. Leukocyte kinetics in pulmonary microcirculation: intravital fluorescence microscopic study. J Appl Physiol (1985) 76 : 6571.
128. Puga I,, Cols M,, Barra CM,, He B,, Cassis L,, Gentile M,, Comerma L,, Chorny A,, Shan M,, Xu W,, Magri G,, Knowles DM,, Tam W,, Chiu A,, Bussel JB,, Serrano S,, Lorente JA,, Bellosillo B,, Lloreta J,, Juanpere N,, Alameda F,, Baro T,, de Heredia CD,, Toran N,, Catala A,, Torrebadell M,, Fortuny C,, Cusi V,, Carreras C,, Diaz GA,, Blander JM,, Farber C,, Silvestri G,, Cunningham-Rundles C,, Calvillo M,, Dufour C,, Notarangelo LD,, Lougaris V,, Plebani A,, Casanova J,, Ganal SC,, Diefenbach A,, Arostegui JI,, Juan M,, Yague J,, Mahlaoui N,, Donadieu J,, Chen K,, Cerutti A . 2011. B cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen. Nat Immunol 13 : 170180.
129. Ng LG,, Qin JS,, Roediger B,, Wang Y,, Jain R,, Cavanagh LL,, Smith AL,, Jones CA,, de Veer M,, Grimbaldeston MA,, Meeusen EN,, Weninger W . 2011. Visualizing the neutrophil response to sterile tissue injury in mouse dermis reveals a three-phase cascade of events. J Invest Dermatol 131 : 20582068.
130. Davies LC,, Jenkins SJ,, Allen JE,, Taylor PR . 2013. Tissue-resident macrophages. Nat Immunol 14 : 986995.
131. Ginhoux F,, Guilliams M . 2016. Tissue-resident macrophage ontogeny and homeostasis. Immunity 44 : 439449.
132. Lavin Y,, Mortha A,, Rahman A,, Merad M . 2015. Regulation of macrophage development and function in peripheral tissues. Nat Rev Immunol 15 : 731744.
133. Lavin Y,, Winter D,, Blecher-Gonen R,, David E,, Keren-Shaul H,, Merad M,, Jung S,, Amit I . 2014. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159 : 13121326.
134. Davalos D,, Grutzendler J,, Yang G,, Kim JV,, Zuo Y,, Jung S,, Littman DR,, Dustin ML,, Gan WB . 2005. ATP mediates rapid microglial response to local brain injury in vivo . Nat Neurosci 8 : 752758.
135. Hines DJ,, Hines RM,, Mulligan SJ,, Macvicar BA . 2009. Microglia processes block the spread of damage in the brain and require functional chloride channels. Glia 57 : 16101618.
136. Saijo K,, Glass CK . 2011. Microglial cell origin and phenotypes in health and disease. Nat Rev Immunol 11 : 775787.
137. Masuda T,, Croom D,, Hida H,, Kirov SA . 2011. Capillary blood flow around microglial somata determines dynamics of microglial processes in ischemic conditions. Glia 59 : 17441753.
138. Wake H,, Moorhouse AJ,, Jinno S,, Kohsaka S,, Nabekura J . 2009. Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J Neurosci 29 : 39743980.
139. Meyer-Luehmann M,, Spires-Jones TL,, Prada C,, Garcia-Alloza M,, de Calignon A,, Rozkalne A,, Koenigsknecht-Talboo J,, Holtzman DM,, Bacskai BJ,, Hyman BT . 2008. Rapid appearance and local toxicity of amyloid-β plaques in a mouse model of Alzheimer’s disease. Nature 451 : 720724.
140. Fuhrmann M,, Bittner T,, Jung CK,, Burgold S,, Page RM,, Mitteregger G,, Haass C,, LaFerla FM,, Kretzschmar H,, Herms J . 2010. Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer’s disease. Nat Neurosci 13 : 411413.
141. Nayak D,, Zinselmeyer BH,, Corps KN,, McGavern DB . 2012. In vivo dynamics of innate immune sentinels in the CNS. Intravital 1 : 95106.
142. Surewaard BGD,, Deniset JF,, Zemp FJ,, Amrein M,, Otto M,, Conly J,, Omri A,, Yates RM,, Kubes P . 2016. Identification and treatment of the Staphylococcus aureus reservoir in vivo. J Exp Med 213 : 11411151.
143. Wong CH,, Jenne CN,, Petri B,, Chrobok NL,, Kubes P . 2013. Nucleation of platelets with blood-borne pathogens on Kupffer cells precedes other innate immunity and contributes to bacterial clearance. Nat Immunol 14 : 785792.
144. Zeng Z,, Surewaard BG,, Wong CH,, Geoghegan JA,, Jenne CN,, Kubes P . 2016. CRIg functions as a macrophage pattern recognition receptor to directly bind and capture blood-borne Gram-positive bacteria. Cell Host Microbe 20 : 99106.
145. Helmy KY,, Katschke KJ Jr,, Gorgani NN,, Kljavin NM,, Elliott JM,, Diehl L,, Scales SJ,, Ghilardi N,, van Lookeren Campagne M . 2006. CRIg: a macrophage complement receptor required for phagocytosis of circulating pathogens. Cell 124 : 915927.
146. Gül N,, Babes L,, Siegmund K,, Korthouwer R,, Bögels M,, Braster R,, Vidarsson G,, ten Hagen TL,, Kubes P,, van Egmond M . 2014. Macrophages eliminate circulating tumor cells after monoclonal antibody therapy. J Clin Invest 124 : 812823.
147. Montalvao F,, Garcia Z,, Celli S,, Breart B,, Deguine J,, Van Rooijen N,, Bousso P . 2013. The mechanism of anti-CD20-mediated B cell depletion revealed by intravital imaging. J Clin Invest 123 : 50985103.
148. McDonald B,, Jenne CN,, Zhuo L,, Kimata K,, Kubes P . 2013. Kupffer cells and activation of endothelial TLR4 coordinate neutrophil adhesion within liver sinusoids during endotoxemia. Am J Physiol Gastrointest Liver Physiol 305 : G797G806.
149. Beattie L,, Peltan A,, Maroof A,, Kirby A,, Brown N,, Coles M,, Smith DF,, Kaye PM . 2010. Dynamic imaging of experimental Leishmania donovani-induced hepatic granulomas detects Kupffer cell-restricted antigen presentation to antigen-specific CD8 T cells. PLoS Pathog 6 : e1000805. doi:10.1371/journal.ppat.1000805.
150. Heymann F,, Peusquens J,, Ludwig-Portugall I,, Kohlhepp M,, Ergen C,, Niemietz P,, Martin C,, van Rooijen N,, Ochando JC,, Randolph GJ,, Luedde T,, Ginhoux F,, Kurts C,, Trautwein C,, Tacke F . 2015. Liver inflammation abrogates immunological tolerance induced by Kupffer cells. Hepatology 62 : 279291.
151. Greter M,, Lelios I,, Pelczar P,, Hoeffel G,, Price J,, Leboeuf M,, Kündig TM,, Frei K,, Ginhoux F,, Merad M,, Becher B . 2012. Stroma-derived interleukin-34 controls the development and maintenance of Langerhans cells and the maintenance of microglia. Immunity 37 : 10501060.
152. Satpathy AT,, Wu X,, Albring JC,, Murphy KM . 2012. Re(de)fining the dendritic cell lineage. Nat Immunol 13 : 11451154.
153. Wang Y,, Szretter KJ,, Vermi W,, Gilfillan S,, Rossini C,, Cella M,, Barrow AD,, Diamond MS,, Colonna M . 2012. IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat Immunol 13 : 753760.
154. Kissenpfennig A,, Henri S,, Dubois B,, Laplace-Builhé C,, Perrin P,, Romani N,, Tripp CH,, Douillard P,, Leserman L,, Kaiserlian D,, Saeland S,, Davoust J,, Malissen B . 2005. Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. Immunity 22 : 643654.
155. Vishwanath M,, Nishibu A,, Saeland S,, Ward BR,, Mizumoto N,, Ploegh HL,, Boes M,, Takashima A . 2006. Development of intravital intermittent confocal imaging system for studying Langerhans cell turnover. J Invest Dermatol 126 : 24522457.
156. Nishibu A,, Ward BR,, Jester JV,, Ploegh HL,, Boes M,, Takashima A . 2006. Behavioral responses of epidermal Langerhans cells in situ to local pathological stimuli. J Invest Dermatol 126 : 787796.
157. Nishibu A,, Ward BR,, Boes M,, Takashima A . 2007. Roles for IL-1 and TNFα in dynamic behavioral responses of Langerhans cells to topical hapten application. J Dermatol Sci 45 : 2330.
158. Kubo A,, Nagao K,, Yokouchi M,, Sasaki H,, Amagai M . 2009. External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers. J Exp Med 206 : 29372946.
159. Ouchi T,, Kubo A,, Yokouchi M,, Adachi T,, Kobayashi T,, Kitashima DY,, Fujii H,, Clausen BE,, Koyasu S,, Amagai M,, Nagao K . 2011. Langerhans cell antigen capture through tight junctions confers preemptive immunity in experimental staphylococcal scalded skin syndrome. J Exp Med 208 : 26072613.
160. Gaiser MR,, Lämmermann T,, Feng X,, Igyarto BZ,, Kaplan DH,, Tessarollo L,, Germain RN,, Udey MC . 2012. Cancer-associated epithelial cell adhesion molecule (EpCAM; CD326) enables epidermal Langerhans cell motility and migration in vivo. Proc Natl Acad Sci U S A 109 : E889E897.
161. Kaplan DH,, Jenison MC,, Saeland S,, Shlomchik WD,, Shlomchik MJ . 2005. Epidermal Langerhans cell-deficient mice develop enhanced contact hypersensitivity. Immunity 23 : 611620.
162. Abtin A,, Jain R,, Mitchell AJ,, Roediger B,, Brzoska AJ,, Tikoo S,, Cheng Q,, Ng LG,, Cavanagh LL,, von Andrian UH,, Hickey MJ,, Firth N,, Weninger W . 2014. Perivascular macrophages mediate neutrophil recruitment during bacterial skin infection. Nat Immunol 15 : 4553.
163. Bain CC,, Scott CL,, Uronen-Hansson H,, Gudjonsson S,, Jansson O,, Grip O,, Guilliams M,, Malissen B,, Agace WW,, Mowat AM . 2013. Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6Chi monocyte precursors. Mucosal Immunol 6 : 498510.
164. Rivollier A,, He J,, Kole A,, Valatas V,, Kelsall BL . 2012. Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon. J Exp Med 209 : 139155.
165. Tamoutounour S,, Henri S,, Lelouard H,, de Bovis B,, de Haar C,, van der Woude CJ,, Woltman AM,, Reyal Y,, Bonnet D,, Sichien D,, Bain CC,, Mowat AM,, Reis e Sousa C,, Poulin LF,, Malissen B,, Guilliams M . 2012. CD64 distinguishes macrophages from dendritic cells in the gut and reveals the Th1-inducing role of mesenteric lymph node macrophages during colitis. Eur J Immunol 42 : 31503166.
166. Chieppa M,, Rescigno M,, Huang AY,, Germain RN . 2006. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J Exp Med 203 : 28412852.
167. Niess JH,, Brand S,, Gu X,, Landsman L,, Jung S,, McCormick BA,, Vyas JM,, Boes M,, Ploegh HL,, Fox JG,, Littman DR,, Reinecker HC . 2005. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307 : 254258.
168. Farache J,, Koren I,, Milo I,, Gurevich I,, Kim KW,, Zigmond E,, Furtado GC,, Lira SA,, Shakhar G . 2013. Luminal bacteria recruit CD103+ dendritic cells into the intestinal epithelium to sample bacterial antigens for presentation. Immunity 38 : 581595.
169. Schulz O,, Jaensson E,, Persson EK,, Liu X,, Worbs T,, Agace WW,, Pabst O . 2009. Intestinal CD103+, but not CX3CR1+, antigen sampling cells migrate in lymph and serve classical dendritic cell functions. J Exp Med 206 : 31013114.
170. Morris DG,, Huang X,, Kaminski N,, Wang Y,, Shapiro SD,, Dolganov G,, Glick A,, Sheppard D . 2003. Loss of integrin αvβ6-mediated TGF-β activation causes Mmp12-dependent emphysema. Nature 422 : 169173.
171. Snelgrove RJ,, Goulding J,, Didierlaurent AM,, Lyonga D,, Vekaria S,, Edwards L,, Gwyer E,, Sedgwick JD,, Barclay AN,, Hussell T . 2008. A critical function for CD200 in lung immune homeostasis and the severity of influenza infection. Nat Immunol 9 : 10741083.
172. Archambaud C,, Salcedo SP,, Lelouard H,, Devilard E,, de Bovis B,, Van Rooijen N,, Gorvel JP,, Malissen B . 2010. Contrasting roles of macrophages and dendritic cells in controlling initial pulmonary Brucella infection. Eur J Immunol 40 : 34583471.
173. Tate MD,, Pickett DL,, van Rooijen N,, Brooks AG,, Reading PC . 2010. Critical role of airway macrophages in modulating disease severity during influenza virus infection of mice. J Virol 84 : 75697580.
174. Varol C,, Mildner A,, Jung S . 2015. Macrophages: development and tissue specialization. Annu Rev Immunol 33 : 643675.
175. Hasegawa A,, Hayashi K,, Kishimoto H,, Yang M,, Tofukuji S,, Suzuki K,, Nakajima H,, Hoffman RM,, Shirai M,, Nakayama T . 2010. Color-coded real-time cellular imaging of lung T-lymphocyte accumulation and focus formation in a mouse asthma model. J Allergy Clin Immunol 125 : 461468.e6. doi:10.1016/j.jaci.2009.09.016.
176. Kiefmann R,, Rifkind JM,, Nagababu E,, Bhattacharya J . 2008. Red blood cells induce hypoxic lung inflammation. Blood 111 : 52055214.
177. Tabuchi A,, Mertens M,, Kuppe H,, Pries AR,, Kuebler WM . 2008. Intravital microscopy of the murine pulmonary microcirculation. J Appl Physiol 1985 104 : 338346.
178. Westphalen K,, Gusarova GA,, Islam MN,, Subramanian M,, Cohen TS,, Prince AS,, Bhattacharya J . 2014. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity. Nature 506 : 503506.
179. Hanna RN,, Cekic C,, Sag D,, Tacke R,, Thomas GD,, Nowyhed H,, Herrley E,, Rasquinha N,, McArdle S,, Wu R,, Peluso E,, Metzger D,, Ichinose H,, Shaked I,, Chodaczek G,, Biswas SK,, Hedrick CC . 2015. Patrolling monocytes control tumor metastasis to the lung. Science 350 : 985990.
180. Carrasco YR,, Batista FD . 2007. B cells acquire particulate antigen in a macrophage-rich area at the boundary between the follicle and the subcapsular sinus of the lymph node. Immunity 27 : 160171.
181. Hickman HD,, Li L,, Reynoso GV,, Rubin EJ,, Skon CN,, Mays JW,, Gibbs J,, Schwartz O,, Bennink JR,, Yewdell JW . 2011. Chemokines control naive CD8+ T cell selection of optimal lymph node antigen presenting cells. J Exp Med 208 : 25112524.
182. Junt T,, Moseman EA,, Iannacone M,, Massberg S,, Lang PA,, Boes M,, Fink K,, Henrickson SE,, Shayakhmetov DM,, Di Paolo NC,, van Rooijen N,, Mempel TR,, Whelan SP,, von Andrian UH . 2007. Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. Nature 450 : 110114.
183. Sagoo P,, Garcia Z,, Breart B,, Lemaître F,, Michonneau D,, Albert ML,, Levy Y,, Bousso P . 2016. In vivo imaging of inflammasome activation reveals a subcapsular macrophage burst response that mobilizes innate and adaptive immunity. Nat Med 22 : 6471.
184. Phan TG,, Green JA,, Gray EE,, Xu Y,, Cyster JG . 2009. Immune complex relay by subcapsular sinus macrophages and noncognate B cells drives antibody affinity maturation. Nat Immunol 10 : 786793.
185. Phan TG,, Grigorova I,, Okada T,, Cyster JG . 2007. Subcapsular encounter and complement-dependent transport of immune complexes by lymph node B cells. Nat Immunol 8 : 9921000.
186. Moalli F,, Proulx ST,, Schwendener R,, Detmar M,, Schlapbach C,, Stein JV . 2015. Intravital and whole-organ imaging reveals capture of melanoma-derived antigen by lymph node subcapsular macrophages leading to widespread deposition on follicular dendritic cells. Front Immunol 6 : 114. doi:10.3389/fimmu.2015.00114.
187. Park C,, Arthos J,, Cicala C,, Kehrl JH . 2015. The HIV-1 envelope protein gp120 is captured and displayed for B cell recognition by SIGN-R1+ lymph node macrophages