Chapter 11 : Leukocyte Chemotaxis

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

Leukocyte Chemotaxis, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816650/9781555814014_Chap11-1.gif /docserver/preview/fulltext/10.1128/9781555816650/9781555814014_Chap11-2.gif


The sequential and regulated recruitment of leukocytes into tissues by chemoattractants is essential for effective clearance of pathogens and healing. The Rho GTPases Cdc42, Rac, and Rho are important for establishing and maintaining migratory polarity. Most chemoattractants for phagocytes signal either through seven transmembrane G-protein-coupled receptors (GPCRs) or tyrosine kinase receptors. Y721 is the most important for chemotaxis because it recruits phospholipase-C-γ (PL C-γ) and the p85 subunit of class 1A PI3Ks, both of which are implicated in the initiation of chemotaxis. Several intracellular signaling complexes contribute to the polarization of phagocytes in response to chemoattractants, and they probably act together to allow optimal chemotaxis. Cdc42 is implicated in multiple types of cell polarity, including axon specification, yeast mating, and epithelial polarity. There are several PLC isoforms, of which PLCβ2 and PLCβ3 are activated by GPCR signaling in neutrophils, whereas PLCβ isoforms are activated by tyrosine kinase receptors. Polarity signals act to initiate polarization of cells, but subsequent maintenance of polarity could be achieved by Rac and Rho without the requirement for additional signals. Rho and Rac refine each other’s activity during cell polarization and migration, balancing actin polymerization, cell contraction, and adhesion essential for chemotaxis. Our current understanding of chemotaxis indicates that several signaling pathways act in concert to induce cell polarization, including Cdc42, Par proteins, PAK/PIX, and PI3Ks. The design and testing of inhibitors of signal transduction molecules involved in migration and chemotaxis will be an important goal for the future.

Citation: Wheeler A, Ridley A. 2009. Leukocyte Chemotaxis, p 183-192. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch11
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Rho GTPase signaling in migration and chemotaxis. (Top) Rho family GTPases cycle between an active GTP-bound conformation and an inactive GDP-bound conformation. This is regulated by RhoGEFs, which stimulate exchange of GDP for GTP, and RhoGAPs, which stimulate hydrolysis of GTP. When bound to GTP, Rho GTPases activate downstream effectors that mediate cellular responses. (Bottom) In migrating cells, Rac is active at the front of cells. Rac is required for lamellipodium extension. Rho activity is restricted mostly to the rear and is involved in generation of cell traction in the cell body and retraction of the tail or uropod.

Citation: Wheeler A, Ridley A. 2009. Leukocyte Chemotaxis, p 183-192. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

GPCR-induced signaling in chemotaxis. Ligand binding to GPCRs activates heterotrimeric G proteins, leading to dissociation of Gα from Gβγ subunits. Gα and Gβγ each activate a variety of signaling pathways that contribute to cell migration. For example, Gα subunits can activate RhoGEFs to increase Rho activity at the rear, and Gβγ subunits activate PI3Kγ, which acts at the front of the cell to stimulate Rac.

Citation: Wheeler A, Ridley A. 2009. Leukocyte Chemotaxis, p 183-192. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

CSF-1 receptor signaling in chemotaxis. Activation of the CSF-1 receptor results in homodimerization (not depicted) and autophosphorylation on several tyrosines. Phosphorylation of Y721 is probably most important for chemotaxis because it recruits PLC-γ and the p85 subunit of class 1A PI3Ks, both of which are implicated in the initiation of chemotaxis. Several other SH2-containing proteins are also recruited to the activated CSF-1 receptor including RhoGEFS and GAPs. KD, kinase domain.

Citation: Wheeler A, Ridley A. 2009. Leukocyte Chemotaxis, p 183-192. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4

Involvement of PI3Ks and PTEN in chemotaxis. PI3Ks are selectively active at the front of polarized migrating cells, whereas PTEN is primarily localized in the cytoplasm. Production of PIP by PI3Ks recruits proteins that have PH domains including the serine/threonine kinase AKT, RhoGEFs, and adaptor proteins such as Gab1, all of which transduce signals to cell motility and chemotaxis. PIP is removed by the phosphatase PTEN, which converts PIP to PI(4,5)P.

Citation: Wheeler A, Ridley A. 2009. Leukocyte Chemotaxis, p 183-192. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Abercrombie, M.,, G. A. Dunn, and, J. P. Heath. 1977. The shape and movement of fibroblasts in culture. Soc. Gen. Physiol. Ser. 32:5770.
2. Adamson, P.,, C. J. Marshall,, A. Hall, and, P. A. Tilbrook. 1992. Post-translational modifications of p21rho proteins. J. Biol. Chem. 267:2003320038.
3. Albelda, S. M.,, C. W. Smith, and, P. A. Ward. 1994. Adhesion molecules and inflammatory injury. FASEB J. 8:504512.
4. Allen, W. E.,, G. E. Jones,, J. W. Pollard, and, A. J. Ridley. 1997. Rho, Rac and Cdc42 regulate actin organization and cell adhesion in macrophages. J. Cell Sci. 110:707720.
5. Allen, W. E.,, D. Zicha,, A. J. Ridley, and, G. E. Jones. 1998. A role for Cdc42 in macrophage chemotaxis. J. Cell Biol. 141:11471157.
6. Arai, H.,, and I. F. Charo. 1996. Differential regulation of G-protein-mediated signaling by chemokine receptors. J. Biol. Chem. 271:2181421819.
7. Bhatt, N. Y.,, T. W. Kelley,, V. V. Khramtsov,, Y. Wang,, G. K. Lam,, T. L. Clanton, and, C. B. Marsh. 2002. Macrophage-colony-stimulating factor-induced activation of extracellular-regulated kinase involves phosphatidylinositol 3-kinase and reactive oxygen species in human monocytes. J. Immunol. 169:64276434.
8. Bokoch, G. M. 2003. Biology of the P21-activated kinases. Annu. Rev. Biochem. 72:743781.
9. Bokoch, G. M. 2005. Regulation of innate immunity by Rho GTPases. Trends Cell Biol. 15:163171.
10. Bompard, G.,, S. J. Sharp,, G. Freiss, and, L. M. Machesky. 2005. Involvement of Rac in actin cytoskeleton rearrangements induced by MIM-B. J. Cell Sci. 118:53935403.
11. Bourette, R. P.,, and L. R. Rohrschneider. 2000. Early events in M-CSF receptor signaling. Growth Factors 17:155166.
12. Bourne, H. R.,, and O. Weiner. 2002. A chemical compass. Nature 419:21.
13. Brach, M. A.,, R. Henschler,, R. H. Mertelsmann, and, F. Herrmann. 1991. Regulation of M-CSF expression by MCSF: role of protein kinase C and transcription factor NFκB. Pathobiology 59:284288.
14. Briggs, M. W.,, and D. B. Sacks. 2003. IQGAP1 as signal integrator: Ca2+, calmodulin, Cdc42 and the cytoskeleton. FEBS Lett. 542:711.
15. Burke, B.,, and C. E. Lewis. 2002. The Macrophage. Oxford University Press, Oxford, United Kingdom.
16. Burke, B.,, S. Sumner,, N. Maitland, and, C. E. Lewis. 2002. Macrophages in gene therapy: cellular delivery vehicles and in vivo targets. J. Leukoc. Biol. 72:417428.
17. Burns, S.,, S. J. Hardy,, J. Buddle,, K. L. Yong,, G. E. Jones, and, A. J. Thrasher. 2004. Maturation of DC is associated with changes in motile characteristics and adherence. Cell Motil. Cytoskeleton 57:118132.
18. Burns, S.,, A. J. Thrasher,, M. P. Blundell,, L. Machesky, and, G. E. Jones. 2001. Configuration of human dendritic cell cytoskeleton by Rho GTPases, the WAS protein, and differentiation. Blood 98:11421149.
19. Burridge, K.,, and R. Doughman. 2006. Front and back by Rho and Rac. Nat. Cell Biol. 8:781782.
20. Calle, Y.,, H. C. Chou,, A. J. Thrasher, and, G. E. Jones. 2004. Wiskott-Aldrich syndrome protein and the cytoskeletal dynamics of dendritic cells. J. Pathol. 204:460469.
21. Carnevale, K. A.,, and M. K. Cathcart. 2001. Calcium-independent phospholipase A(2) is required for human monocyte chemotaxis to monocyte chemoattractant protein 1. J. Immunol. 167:34143421.
22. Chellaiah, M. A.,, N. Soga,, S. Swanson,, S. McAllister,, U. Alvarez,, D. Wang,, S. F. Dowdy, and, K. A. Hruska. 2000. Rho-A is critical for osteoclast podosome organization, motility, and bone resorption. J. Biol. Chem. 275:1199312002.
23. Chen, L.,, M. Iijima,, M. Tang,, M. A. Landree,, Y. E. Huang,, Y. Xiong,, P. A. Iglesias, and, P. N. Devreotes. 2007. PLA2 and PI3K/PTEN pathways act in parallel to mediate chemotaxis. Dev. Cell 12:603614.
24. Civelekoglu-Scholey, G.,, A. Wayne Orr,, I. Novak,, J. J. Meister,, M. A. Schwartz, and, A. Mogilner. 2005. Model of coupled transient changes of Rac, Rho, adhesions and stress fibers alignment in endothelial cells responding to shear stress. J. Theor. Biol. 232:569585.
25. Colucci-Guyon, E.,, F. Niedergang,, B. J. Wallar,, J. Peng,, A. S. Alberts, and, P. Chavrier. 2005. A role for mammalian diaphanous-related formins in complement receptor (CR3)-mediated phagocytosis in macrophages. Curr. Biol. 15:20072012.
26. Eddy, R. J.,, L. M. Pierini,, F. Matsumura, and, F. R. Maxfield. 2000. Ca2+-dependent myosin II activation is required for uropod retraction during neutrophil migration. J. Cell Sci. 113:12871298.
27. Eisenmann, K. M.,, E. S. Harris,, S. M. Kitchen,, H. A. Holman,, H. N. Higgs, and, A. S. Alberts. 2007. Dia-interacting protein modulates formin-mediated actin assembly at the cell cortex. Curr. Biol. 17:579591.
28. Eng, E. W.,, A. Bettio,, J. Ibrahim, and, R. E. Harrison. 2007. MTOC reorientation occurs during FcγR-mediated phagocytosis in macrophages. Mol. Biol. Cell 18:2389-2399.
29. Etienne-Manneville, S. 2004. Cdc42—the centre of polarity. J. Cell Sci. 117:12911300.
30. Ferguson, G. J.,, L. Milne,, S. Kulkarni,, T. Sasaki,, S. Walker,, S. Andrews,, T. Crabbe,, P. Finan,, G. Jones,, S. Jackson,, M. Camps,, C. Rommel,, M. Wymann,, E. Hirsch,, P. Hawkins, and, L. Stephens. 2007. PI(3)Kγ has an important context-dependent role in neutrophil chemokinesis. Nat. Cell Biol. 9:8691.
31. Franca-Koh, J.,, Y. Kamimura, and, P. Devreotes. 2006. Navigating signaling networks: chemotaxis in Dictyostelium discoideum. Curr. Opin. Genet. Dev. 16:333338.
32. Friedl, P. 2004. Prespecification and plasticity: shifting mechanisms of cell migration. Curr. Opin. Cell Biol. 16:1423.
33. Funamoto, S.,, R. Meili,, S. Lee,, L. Parry, and, R. A. Firtel. 2002. Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis. Cell 109:611623.
34. Gakidis, M. A. M.,, X. Cullere,, T. Olson,, J. L. Wilsbacher,, B. Zhang,, S. L. Moores,, K. Ley,, W. Swat,, T. Mayadas, and, J. S. Brugge. 2004. Vav GEFs are required for β2 integrin-dependent functions of neutrophils. J. Cell Biol. 166:273282.
35. Gardiner, E. M.,, K. N. Pestonjamasp,, B. P. Bohl,, C. Chamberlain,, K. M. Hahn, and, G. M. Bokoch. 2002. Spatial and temporal analysis of Rac activation during live neutrophil chemotaxis. Curr. Biol. 12:20292034.
36. Glantschnig, H.,, J. E. Fisher,, G. Wesolowski,, G. A. Rodan, and, A. A. Reszka. 2003. M-CSF, TNFalpha and RANK ligand promote osteoclast survival by signaling through mTOR/S6 kinase. Cell Death Differ. 10:11651177.
37. Glogauer, M.,, C. C. Marchal,, F. Zhu,, A. Worku,, B. E. Clausen,, I. Foerster,, P. Marks,, G. P. Downey,, M. Dinauer, and, D. J. Kwiatkowski. 2003. Rac1 deletion in mouse neutrophils has selective effects on neutrophil functions. J. Immunol. 170:56525657.
38. Hannigan, M.,, L. Zhan,, Z. Li,, Y. Ai,, D. Wu, and, C. K. Huang. 2002. Neutrophils lacking phosphoinositide 3-kinase gamma show loss of directionality during N-formyl-Met-Leu-Phe-induced chemotaxis. Proc. Natl. Acad. Sci. USA 99:36033608.
39. Henderson, R. B.,, J. A. Hobbs,, M. Mathies, and, N. Hogg. 2003. Rapid recruitment of inflammatory monocytes is independent of neutrophil migration. Blood 102:328335.
40. Higgs, H. N.,, and T. D. Pollard. 1999. Regulation of actin polymerization by Arp2/3 complex and WASp/Scar proteins. J. Biol. Chem. 274:3253132534.
41. Huang, Y. E.,, M. Iijima,, C. A. Parent,, S. Funamoto,, R. A. Firtel, and, P. Devreotes. 2003. Receptor-mediated regulation of PI3Ks confines PI(3,4,5)P3 to the leading edge of chemotaxing cells. Mol. Biol. Cell 14:19131922.
42. Ishizaki, T.,, Y. Morishima,, M. Okamoto,, T. Furuyashiki,, T. Kato, and, S. Narumiya. 2001. Coordination of microtubules and the actin cytoskeleton by the Rho effector mDia1. Nat. Cell Biol. 3:814.
43. Jimenez-Sainz, M. C.,, B. Fast,, F. Mayor, Jr., and, A. M. Aragay. 2003. Signaling pathways for monocyte chemoattractant protein 1-mediated extracellular signal-regulated kinase activation. Mol. Pharmacol. 64:773782.
44. Jones, G. E.,, E. Prigmore,, R. Calvez,, C. Hogan,, G. A. Dunn,, E. Hirsch,, M. P. Wymann, and, A. J. Ridley. 2003. Requirement for PI 3-kinase γ in macrophage migration to MCP-1 and CSF-1. Exp. Cell Res. 290:120131.
45. Jones, G. E.,, D. Zicha,, G. A. Dunn,, M. Blundell, and, A. Thrasher. 2002. Restoration of podosomes and chemotaxis in Wiskott-Aldrich syndrome macrophages following induced expression of WASp. Int. J. Biochem. Cell Biol. 34:806815.
46. Kelley, T. W.,, M. M. Graham,, A. I. Doseff,, R. W. Pomerantz,, S. M. Lau,, M. C. Ostrowski,, T. F. Franke, and, C. B. Marsh. 1999. Macrophage colony-stimulating factor promotes cell survival through Akt/protein kinase B. J. Biol. Chem. 274:2639326398.
47. Kobayashi, H.,, S. Miura,, H. Nagata,, Y. Tsuzuki,, R. Hokari,, T. Ogino,, C. Watanabe,, T. Azuma, and, H. Ishii. 2004. In situ demonstration of dendritic cell migration from rat intestine to mesenteric lymph nodes: relationships to maturation and role of chemokines. J. Leukoc. Biol. 75:434442.
48. Kobayashi, Y. 2008. The role of chemokines in neutrophil biology. Front. Biosci. 13:24002407.
49. Koike, D.,, H. Obinata,, A. Yamamoto,, S. Takeda,, H. Komori,, F. Nara,, T. Izumi, and, T. Haga. 2006. 5-Oxoeicosatetraenoic acid-induced chemotaxis: identification of a responsible receptor hGPCR48 and negative regulation by G protein G12/13. J. Biochem. (Tokyo) 139:543549.
50. Lacalle, R. A.,, C. Gomez-Mouton,, D. F. Barber,, S. Jimenez-Baranda,, E. Mira,, C. Martinez-A,, A. C. Carrera, and, S. Manes. 2004. PTEN regulates motility but not directionality during leukocyte chemotaxis. J. Cell Sci. 117:62076215.
51. Lattin, J.,, D. A. Zidar,, K. Schroder,, S. Kellie,, D. A. Hume, and, M. J. Sweet. 2007. G-protein-coupled receptor expression, function, and signaling in macrophages. J. Leukoc. Biol. 82:1632.
52. Li, S.,, A. Yamauchi,, C. C. Marchal,, J. K. Molitoris,, L. A. Quilliam, and, M. C. Dinauer. 2002. Chemoattractant-stimulated Rac activation in wild-type and Rac2-deficient murine neutrophils: preferential activation of Rac2 and Rac2 gene dosage effect on neutrophil functions. J. Immunol. 169:50435051.
53. Li, Z.,, X. Dong,, Z. Wang,, W. Liu,, N. Deng,, Y. Ding,, L. Tang,, T. Hla,, R. Zeng,, L. Li, and, D. Wu. 2005. Regulation of PTEN by Rho small GTPases. Nat. Cell Biol. 7:399404.
54. Li, Z.,, M. Hannigan,, Z. Mo,, B. Liu,, W. Lu,, Y. Wu,, A. V. Smrcka,, G. Wu,, L. Li,, M. Liu,, C. K. Huang, and, D. Wu. 2003. Directional sensing requires G beta gamma-mediated PAK1 and PIX alpha-dependent activation of Cdc42. Cell 114:215227.
55. Li, Z.,, H. Jiang,, W. Xie,, Z. Zhang,, A. V. Smrcka, and, D. Wu. 2000. Roles of PLC-2 and -3 and PI3K in chemoattractant-mediated signal transduction. Science 287:10461049.
56. Linder, S.,, and M. Aepfelbacher. 2003. Podosomes: adhesion hot-spots of invasive cells. Trends Cell Biol. 13:376385.
57. Locati, M.,, G. Lamorte,, W. Luini,, M. Introna,, S. Bernasconi,, A. Mantovani, and, S. Sozzani. 1996. Inhibition of monocyte chemotaxis to C-C chemokines by antisense oligonucleotide for cytosolic phospholipase A2. J. Biol. Chem. 271:60106016.
58. Lu, B.,, B. J. Rutledge,, L. Gu,, J. Fiorillo,, N. W. Lukacs,, S. L. Kunkel,, R. North,, C. Gerard, and, B. J. Rollins. 1998. Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice. J. Exp. Med. 187:601608.
59. Mahadeo, D. C.,, M. Janka-Junttila,, R. L. Smoot,, P. Rose-lova, and, C. A. Parent. 2007. A chemoattractant-mediated Gi-coupled pathway activates adenylyl cyclase in human neutrophils. Mol. Biol. Cell 18:512522.
60. Matsuoka, S.,, M. Iijima,, T. M. Watanabe,, H. Kuwayama,, T. Yanagida,, P. N. Devreotes, and, M. Ueda. 2006. Single-molecule analysis of chemoattractant-stimulated membrane recruitment of a PH-domain-containing protein. J. Cell Sci. 119:10711079.
61. Merlot, S.,, and R. A. Firtel. 2003. Leading the way: directional sensing through phosphatidylinositol 3-kinase and other signaling pathways. J. Cell Sci. 116:34713478.
62. Miki, H.,, K. Miura, and, T. Takenawa. 1996. N-WASP, a novel actin-depolymerizing protein, regulates the cortical cytoskeletal rearrangement in a PIP2-dependent manner downstream of tyrosine kinases. EMBO J. 15:53265335.
63. Millard, T. H.,, S. J. Sharp, and, L. M. Machesky. 2004. Signalling to actin assembly via the WASP (Wiskott-Aldrich syndrome protein)-family proteins and the Arp2/3 complex. Biochem. J. 380:117.
64. Mitchison, T. J.,, and L. P. Cramer. 1996. Actin-based cell motility and cell locomotion. Cell 84:371379.
65. Myers, S. J.,, L. M. Wong, and, I. F. Charo. 1995. Signal transduction and ligand specificity of the human monocyte chemoattractant protein-1 receptor in transfected embryonic kidney cells. J. Biol. Chem. 270:57865792.
66. Needham, L. K.,, and E. Rozengurt 1998. Galpha12 and Galpha13 stimulate Rho-dependent tyrosine phosphorylation of focal adhesion kinase, paxillin, and p130 Crk-associated substrate. J. Biol. Chem. 273:1462614632.
67. Neves, S.,, P. Ram, and, R. Iyengar. 2002. G protein pathways. Science 296:16361639.
68. Niggli, V. 1999. Rho-kinase in human neutrophils: a role in signalling for myosin light chain phosphorylation and cell migration. FEBS Lett. 445:6972.
69. Niggli, V. 2003. Signaling to migration in neutrophils: importance of localized pathways. Int. J. Biochem. Cell Biol. 35:16191638.
70. Nuzzi, P. A.,, M. A. Senetar, and, A. Huttenlocher. 2007. Asymmetric localization of calpain 2 during neutrophil chemotaxis. Mol. Biol. Cell 18:795805.
71. Palazzo, A. F.,, C. H. Eng,, D. D. Schlaepfer,, E. E. Marcantonio, and, G. G. Gundersen. 2004. Localized stabilization of microtubules by integrin- and FAK-facilitated Rho signaling. Science 303:836839.
72. Palazzo, A. F.,, H. L. Joseph,, Y. J. Chen,, D. L. Dujardin,, A. S. Alberts,, K. K. Pfister,, R. B. Vallee, and, G. G. Gundersen. 2001. Cdc42, dynein, and dynactin regulate MTOC reorientation independent of Rho-regulated microtubule stabilization. Curr. Biol. 11:15361541.
73. Pestonjamasp, K. N.,, C. Forster,, C. Sun,, E. M. Gardiner,, B. Bohl,, O. Weiner,, G. M. Bokoch, and, M. Glogauer. 2006. Rac1 links leading edge and uropod events through Rho and myosin activation during chemotaxis. Blood 108:28142820.
74. Pierce, K. L.,, and R. J. Lefkowitz. 2001. Classical and new roles of beta-arrestins in the regulation of G-protein-coupled receptors. Nat. Rev. Neurosci. 2:727733.
75. Pixley, F. J.,, and E. R. Stanley. 2004. CSF-1 regulation of the wandering macrophage: complexity in action. Trends Cell Biol. 14:628638.
76. Postma, M.,, L. Bosgraaf,, H. M. Loovers, and, P. J. Van Haastert. 2004. Chemotaxis: signalling modules join hands at front and tail. EMBO Rep. 5:3540.
77. Procko, E.,, and S. R. McColl. 2005. Leukocytes on the move with phosphoinositide 3-kinase and its downstream effectors. BioEssays 27:153163.
78. Rickert, P.,, O. D. Weiner,, F. Wang,, H. R. Bourne, and, G. Servant. 2000. Leukocytes navigate by compass: roles of PI3Kgamma and its lipid products. Trends Cell Biol. 10:466473.
79. Ridley, A. J. 2004. Rho proteins and cancer. Breast Cancer Res. Treat. 84:1319.
80. Ridley, A. J.,, M. A. Schwartz,, K. Burridge,, R. A. Firtel,, M. H. Ginsberg,, G. Borisy,, J. T. Parsons, and, A. R. Horwitz. 2003. Cell migration: integrating signals from front to back. Science 302:17041709.
81. Riento, K.,, and A. J. Ridley. 2003. Rocks: multifunctional kinases in cell behaviour. Nat. Rev. Mol. Cell Biol. 4:446456.
82. Rohatgi, R.,, L. Ma,, H. Miki,, M. Lopez,, T. Kirchhausen,, T. Takenawa, and, M. W. Kirschner. 1999. The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly. Cell 97:221231.
83. Rot, A.,, and U. H. von Andrian. 2004. Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells. Annu. Rev. Immunol. 22:891928.
84. Rousseau, S.,, I. Dolado,, V. Beardmore,, N. Shpiro,, R. Marquez,, A. R. Nebreda,, J. S. Arthur,, L. M. Case,, M. Tessier-Lavigne,, M. Gaestel,, A. Cuenda, and, P. Cohen. 2006. CXCL12 and C5a trigger cell migration via a PAK1/2-p38α MAPK-MAPKAP-K2-HSP27 pathway. Cell Signal. 18:18971905.
85. Srinivasan, S.,, F. Wang,, S. Glavas,, A. Ott,, F. Hofmann,, K. Aktories,, D. Kalman, and, H. R. Bourne. 2003. Rac and Cdc42 play distinct roles in regulating PI(3,4,5)P3 and polarity during neutrophil chemotaxis. J. Cell Biol. 160:375385.
86. Suetsugu, S.,, K. Murayama,, A. Sakamoto,, K. Hanawa-Suetsugu,, A. Seto,, T. Oikawa,, C. Mishima,, M. Shirouzu,, T. Takenawa, and, S. Yokoyama. 2006. The RAC binding domain/IRSp53-MIM homology domain of IRSp53 induces RAC-dependent membrane deformation. J. Biol. Chem. 281:3534735358.
87. Suire, S.,, A. M. Condliffe,, G. J. Ferguson,, C. D. Ellson,, H. Guillou,, K. Davidson,, H. Welch,, J. Coadwell,, M. Turner,, E. R. Chilvers,, P. T. Hawkins, and, L. Stephens. 2006. Gβγ and the Ras binding domain of p110γ are both important regulators of PI3K[gamma] signalling in neutrophils. Nat. Cell Biol. 8:13031309.
88. Sun, C. X.,, G. P. Downey,, F. Zhu,, A. L. Koh,, H. Thang, and, M. Glogauer. 2004. Rac1 is the small GTPase responsible for regulating the neutrophil chemotaxis compass. Blood 104:37583765.
89. Symons, M.,, J. M. Derry,, B. Karlak,, S. Jiang,, V. Lemahieu,, F. McCormick,, U. Francke, and, A. Abo. 1996. Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization. Cell 84:723734.
90. Takenawa, T.,, and S. Suetsugu. 2007. The WASP-WAVE protein network: connecting the membrane to the cytoskeleton. Nat. Rev. Mol. Cell Biol. 8:3748.
91. Vanhaesebroeck, B.,, G. E. Jones,, W. E. Allen,, D. Zicha,, R. Hooshmand-Rad,, C. Sawyer,, C. Wells,, M. D. Waterfield, and, A. J. Ridley. 1999. Distinct PI(3)Ks mediate mitogenic signalling and cell migration in macrophages. Nat. Cell Biol. 1:6971.
92. Van Keymeulen, A.,, K. Wong,, Z. A. Knight,, C. Govaerts,, K. M. Hahn,, K. M. Shokat, and, H. R. Bourne. 2006. To stabilize neutrophil polarity, PIP3 and Cdc42 augment RhoA activity at the back as well as signals at the front. J. Cell Biol. 174:437445.
93. Watanabe, N.,, P. Madaule,, T. Reid,, T. Ishizaki,, G. Watanabe,, A. Kakizuka,, Y. Saito,, K. Nakao,, B. M. Jockusch, and, S. Narumiya. 1997. p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin. EMBO J. 16:30443056.
94. Watanabe, T.,, J. Noritake, and, K. Kaibuchi. 2005. Regulation of microtubules in cell migration. Trends Cell Biol. 15:7683.
95. Webb, S. E.,, J. W. Pollard, and, G. E. Jones. 1996. Direct observation and quantification of macrophage chemoattraction to the growth factor CSF-1. J. Cell Sci. 109:793803.
96. Weiner, O. D.,, P. O. Neilsen,, G. D. Prestwich,, M. W. Kirschner,, L. C. Cantley, and, H. R. Bourne. 2002. A PtdInsP(3)- and Rho GTPase-mediated positive feedback loop regulates neutrophil polarity. Nat. Cell Biol. 4:509513.
97. Weiss-Haljiti, C.,, C. Pasquali,, H. Ji,, C. Gillieron,, C. Chabert,, M. L. Curchod,, E. Hirsch,, A. J. Ridley,, R. H. van Huijsduijnen,, M. Camps, and, C. Rommel. 2004. Involvement of phosphoinositide 3-kinase gamma, Rac, and PAK signaling in chemokine-induced macrophage migration. J. Biol. Chem. 279:4327343284.
98. Welch, H. C.,, A. M. Condliffe,, L. J. Milne,, G. J. Ferguson,, K. Hill,, L. M. Webb,, K. Okkenhaug,, W. J. Coadwell,, S. R., Andrews,, M. Thelen,, G. E. Jones,, P. T. Hawkins, and, L. R. Stephens. 2005. P-Rex1 regulates neutrophil function. Curr. Biol. 15:18671873.
99. Welch, M. D.,, and R. D. Mullins. 2002. Cellular control of actin nucleation. Annu. Rev. Cell Dev. Biol. 18:247288.
100. Wells, C. M.,, P. J. Bhavsar,, I. R. Evans,, E. Vigorito,, M. Turner,, V. Tybulewicz, and, A. J. Ridley. 2005. Vav1 and Vav2 play different roles in macrophage migration and cytoskeletal organization. Exp. Cell Res. 310:303310.
101. Wells, C. M.,, M. Walmsley,, S. Ooi,, V. Tybulewicz, and, A. J. Ridley. 2004. Rac1-deficient macrophages exhibit defects in cell spreading and membrane ruffling but not migration. J. Cell Sci. 117:12591268.
102. Wennerberg, K.,, and C. J. Der. 2004. Rho-family GTPases: it’s not only Rac and Rho (and I like it). J. Cell Sci. 117:13011312.
103. Wettschureck, N.,, and S. Offermanns. 2005. Mammalian G proteins and their cell type specific functions. Physiol. Rev. 85:11591204.
104. Wheeler, A. P.,, and A. J. Ridley. 2007. RhoB affects macrophage adhesion, integrin expression and migration. Exp. Cell Res. 313:35053516.
105. Wheeler, A. P.,, C. M. Wells,, S. D. Smith,, F. M. Vega,, R. B. Henderson,, V. L. Tybulewicz, and, A. J. Ridley. 2006. Rac1 and Rac2 regulate macrophage morphology but are not essential for migration. J. Cell Sci. 119:27492757.
106. Wong, K.,, O. Pertz,, K. Hahn, and, H. Bourne. 2006. Neutrophil polarization: spatiotemporal dynamics of RhoA activity support a self-organizing mechanism. Proc. Natl. Acad. Sci. USA 103:36393644.
107. Wymann, M. P.,, and L. Pirola. 1998. Structure and function of phosphoinositide 3-kinases. Biochim. Biophys. Acta 1436:127150.
108. Xu, J.,, A. Van Keymeulen,, N. M. Wakida,, P. Carlton,, M. W. Berns, and, H. R. Bourne. 2007. Polarity reveals intrinsic cell chirality. Proc. Natl. Acad. Sci. USA 104:92969300.
109. Xu, J.,, F. Wang,, A. Van Keymeulen,, P. Herzmark,, A. Straight,, K. Kelly,, Y. Takuwa,, N. Sugimoto,, T. Mitchison, and, H. R. Bourne. 2003. Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. Cell 114:201214.
110. Xu, J.,, F. Wang,, A. Van Keymeulen,, M. Rentel, and, H. R. Bourne. 2005. Neutrophil microtubules suppress polarity and enhance directional migration. Proc. Natl. Acad. Sci. USA 102:68846889.
111. Yeung, Y. G.,, and E. R. Stanley. 2003. Proteomic approaches to the analysis of early events in colony-stimulating factor-1 signal transduction. Mol. Cell Proteomics 2:11431155.
112. Yeung, Y. G.,, Y. Wang,, D. B. Einstein,, P. S. Lee, and, E. R. Stanley. 1998. Colony-stimulating factor-1 stimulates the formation of multimeric cytosolic complexes of signaling proteins and cytoskeletal components in macrophages. J. Biol. Chem. 273:1712817137.
113. Zenke, F. T.,, M. Krendel,, C. DerMardirossian,, C. C. King,, B. P. Bohl, and, G. M. Bokoch. 2004. p21-activated kinase 1 phosphorylates and regulates 14-3-3 binding to GEF-H1, a microtubule-localized Rho exchange factor. J. Biol. Chem. 279:1839218400.
114. Zhan, Q.,, J. R. Bamburg, and, J. A. Badwey. 2003. Products of phosphoinositide specific phospholipase C can trigger dephosphorylation of cofilin in chemoattractant stimulated neutrophils. Cell Motil. Cytoskeleton 54:1-15.
115. Zhao, T.,, P. Nalbant,, M. Hoshino,, X. Dong,, D. Wu, and, G. M. Bokoch. 2007. Signaling requirements for translocation of P-Rex1, a key Rac2 exchange factor involved in chemoattractant-stimulated human neutrophil function. J. Leukoc. Biol. 81:11271136.
116. Zlotnik, A.,, and O. Yoshie. 2000. Chemokines: a new classification system and their role in immunity. Immunity 12:121127.


Generic image for table

Chemokine receptors expressed on macrophages and neutrophils

Citation: Wheeler A, Ridley A. 2009. Leukocyte Chemotaxis, p 183-192. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch11

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error