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Chapter 17 : Reactive Oxygen Intermediates, pH, and Calcium

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Abstract:

Reactive oxygen intermediates (ROIs), pH exacerbations, and calcium fluxes can act together to effect fungal killing at the level of the phagocyte; therefore, resilience in the face of rapid environmental alterations is necessary to promote fungal survival within the susceptible host. With such goals in mind the scientific community has pursued an understanding of innate immune defenses against Aspergillus fumigatus spores and hyphae. The threat posed by ROIs to cellular structures and functions is an unavoidable consequence of anaerobic respiration; thus, aerobic organisms have evolved mechanisms to neutralize ROIs resulting from normal physiological processes. The search for an antimicrobial mechanism such as superoxide production by phagocytic cells, had been prompted by several observations. First, dramatic increases in neutrophil oxygen uptake had been observed during phagocytosis of multiple microorganisms. Second, the occurrence of superoxide dismutase enzymes, which provide a cellular defense against the harmful effects of superoxide, was evident in aerobic but not in anaerobic cells. Finally, myeloperoxidase (MPO)-catalyzed peroxidation of halides failed to fully account for the microbicidal activity of leukocytes, as evidenced by the largely asymptomatic presentation of congenital MPO deficiency in humans, suggesting an alternative mechanism of oxygen-dependent microbial killing. A rise in intracellular calcium is not required for uptake of microorganisms through phagocytosis, but it is necessary for killing of ingested prey. Under circumstances in which A. fumigatus escapes from the phagocytic vacuole, appropriate adaptation to the impaired phagolysosomal environment is an important aspect of survival in the host.

Citation: Bignell E. 2009. Reactive Oxygen Intermediates, pH, and Calcium, p 217-228. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch17
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Figures

Image of Figure 1.
Figure 1.

Four-step reduction of molecular oxygen and resulting ROIs. The Lewis dot diagram depicts the stepwise reduction of O2. Complete reduction of molecular oxygen to water involves the addition of four protons and four electrons. The hydroxyl radical is the strongest ROI, being capable of indiscriminate oxidation of organic compounds such as biological macromolecules.

Citation: Bignell E. 2009. Reactive Oxygen Intermediates, pH, and Calcium, p 217-228. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch17
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Image of Figure 2.
Figure 2.

ROI production during phagocytosis. Shown is a schematic view of an A. fumigatus spore during phagocytosis and concomitant generation of ROIs. The spatially segregated NADPH-oxidase molecular components gp91 phox , p22 phox ,p67 phox , p47 phox , p40 phox , and p21 rac -GTP (represented by ovals) assemble into an active NADPH-oxidase complex in the phagosomal membrane of activated phagocytes. Transfer of electrons from cytosolic NADPH to dissolved molecular oxygen at the cell surface (and/or in the forming phagolysosome) generates the highly unstable superoxide anion (O2 -). Dismutation of superoxide (via superoxide dismutase [SOD]) generates hydrogen peroxide (H2O2), a progenitor of HOCl (via MPO-mediated halide oxidation), singlet oxygen (1O2), and hydroxyl radicals (OH7). Microbicidal enzymes are delivered to the phagosome from subcellular organelles called granules, coincident with, or soon after, the phagocytic event.

Citation: Bignell E. 2009. Reactive Oxygen Intermediates, pH, and Calcium, p 217-228. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch17
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Image of Figure 3.
Figure 3.

Schematic representation of plasma and endosomal membrane associations with pH signaling and ESCRT complexes. Molecules having demonstrated roles in pH signaling in S. cerevisae are shaded dark gray. Those leading to partially constitutive pH signaling in S. cerevisiae are shaded light gray. Links between ESCRTs are not shown.

Citation: Bignell E. 2009. Reactive Oxygen Intermediates, pH, and Calcium, p 217-228. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch17
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References

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1. Appelberg, R. 2007. Neutrophils and intracellular pathogens: beyond phagocytosis and killing. Trends Microbiol. 15: 8792.
2. Aratani, Y.,, F. Kura,, H. Watanabe,, H. Akagawa,, Y. Takano,, K. Suzuki,, M. C. Dinauer,, N. Maeda, and, H. Koyama. 2002. Relative contributions of myeloperoxidase and NADPH-oxidase to the early host defense against pulmonary infections with Candida albicans and Aspergillus fumigatus. Med. Mycol. 40: 557563.
3. Arst, H. N., and, M. A. Penalva. 2003. pH regulation in Aspergillus and parallels with higher eukaryotic regulatory systems. Trends Genet. 19: 224231.
4. Babior, B. M. 2004. NADPH oxidase. Curr. Opin. Immunol. 16: 4247.
5. Babior, B. M.,, R. S. Kipnes, and, J. T. Curnutte. 1973. Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J. Clin. Investig. 52: 741744.
6. Bignell, E.,, S. Negrete-Urtasun,, A. M. Calcagno,, H. N. Arst, Jr.,, T. Rogers, and, K. Haynes. 2005. Virulence comparisons of Aspergillus nidulans mutants are confounded by the inflammatory response of p47phox-/- mice lnfect. Immun. 73: 52045207.
7. Bignell, E.,, S. Negrete-Urtasun,, A. M. Calcagno,, K. Haynes,, H. N. Arst, Jr., and, T. Rogers. 2005. The Aspergillus pH-responsive transcription factor PacC regulates virulence. Mol. Microbiol. 55: 10721084.
8. Bok, J. W.,, D. Chung,, S. A. Balajee,, K. A. Marr,, D. Andes,, K. F. Nielsen,, J. C. Frisvad,, K. A. Kirby, and, N. P. Keller. 2006. GliZ, a transcriptional regulator of gliotoxin biosynthesis, contributes to Aspergillus fumigatus virulence. Infect. Immun. 74: 67616768.
9. Borregaard, N.,, O. E. Sorensen, and, K. Theilgaard-Monch. 2007. Neutrophil granules: a library of innate immunity proteins. Trends Immunol. 28: 340345.
10. Boysen, J. H., and, A. P. Mitchell. 2006. Control of Bro1-domain protein Rim20 localization by external pH, ESCRT machinery, and the Saccharomyces cerevisiae Rim101 pathway. Mol. Biol. Cell 17: 340345.
11. Caddick, M. X.,, A. G. Brownlee, and, H. N. Arst, Jr. 1986. Regulation of gene expression by pH of the growth medium in Aspergillus nidulans. Mol. Gen. Genet. 203: 340345.
12. Calcagno-Pizarelli, A. M.,, S. Negrete-Urtasun,, S. H. Denison,, J. D. Rudnicka,, H. J. Bussink,, T. Munera-Huertas,, L. Stanton,, A. Hervas-Aguilar,, E. A. Espeso,, J. Tilburn,, H. N. Arst, Jr., and, M. A. Penalva. 2007. Establishment of the ambient pH signaling complex in Aspergillus nidulans: PalI assists plasma membrane localization of PalH. Eukaryot. Cell 6: 340345.
13. Chang, Y. C,, B. H. Segal,, S. M. Holland,, G. F. Miller, and, K. J. Kwon-Chung. 1998. Virulence of catalase-deficient Aspergillus nidulans in p47phox-/- mice. Implications for fungal pathogenicity and host defense in chronic granulomatous disease. J. Clin. Investig. 101: 340345.
14. Clapham, D. E. 2007. Calcium signaling. Cell 131: 340345.
15. Cramer, R. A., Jr.,, M. P. Gamcsik,, R. M. Brooking,, L. K. Najvar,, W. R. Kirkpatrick,, T. F. Patterson,, C. J. Balibar,, J. R. Graybill,, J. R. Perfect,, S. N. Abraham, and, W. J. Steinbach. 2006. Disruption of a nonribosomal peptide synthetase in Aspergillus fumigatus eliminates gliotoxin production. Eukaryot. Cell 5: 340345.
16. Curnutte, J. T. 2004. Superoxide production by phagocytic leukocytes: the scientific legacy of Bernard Babior. J. Clin. Investig. 114: 340345.
17. Curnutte, J. T.,, D. M. Whitten, and, B. M. Babior. 1974. Defective superoxide production by granulocytes from patients with chronic granulomatous disease. N. Engl. J. Med. 290: 340345.
18. Cyert, M. S. 2003. Calcineurin signalling in Saccharomyces cerevisiae: how yeast go crazy in response to stress. Biochem. Biophys. Res. Commun. 311: 340345.
19. da Silva Ferreira, M. E.,, T. Heinekamp,, A. Hard,, A. A. Brakhage,, C. P. Semighini,, S. D. Harris,, M. Savoldi,, P. F. de Gouvea,, M. H. de Souza Goldman, and, G. H. Goldman. 2007. Functional characterization of the Aspergillus fumigatus calcineurin. Fungal Genet. Biol. 44: 340345.
20. da Silva Ferreira, M. E.,, M. R. Kress,, M. Savoldi,, M. H. Goldman,, A. Hard,, T. Heinekamp,, A. A. Brakhage, and, G. H. Goldman. 2006. The akuBKU80 mutant deficient for nonhomologous end joining is a powerful tool for analyzing pathogenicity in Aspergillus fumigatus. Eukaryot. Cell 5: 207211.
21. Diamond, R. D., and, R. A. Clark. 1982. Damage to Aspergillus fumigatus and Rhizopus oryzae hyphae by oxidative and nonoxidative microbicidal products of human neutrophils in vitro. Infect. Immun. 38: 487495.
22. Diez, E.,, J. Alvaro,, E. A. Espeso,, L. Rainbow,, T. Suarez,, J. Tilburn,, H. N. Arst, Jr., and, M. A. Penalva. 2002. Activation of the Aspergillus PacC zinc finger transcription factor requires two proteolytic steps. EMBO J. 21: 13501359.
23. Dri, P.,, G. Presani,, S. Perticarari,, L. Alberi,, M. Prodan, and, E. Decleva. 2002. Measurement of phagosomal pH of normal and CGD-like human neutrophils by dual fluorescence flow cytometry. Cytometry 48: 159166.
24. Eissenberg, L. G.,, W. E. Goldman, and, P. H. Schlesinger. 1993. Histoplasma capsulatum modulates the acidification of phagolysosomes. J. Exp. Med. 177: 16051611.
25. Fernadez-Martinez, J.,, C. V. Brown,, E. Diez,, J. Tilburn,, H. N. Arst, Jr.,, M. A. Penalva, and, E. A. Espeso. 2003. Overlap of nuclear localisation signal and specific DNA-binding residues within the zinc finger domain of PacC. J. Mol. Biol. 334: 667684.
26. Franklin, R. A.,, O. G. Rodriguez-Mora,, M. M. Lahair, and, J. A. McCubrey. 2006. Activation of the calcium/calmodulin-dependent protein kinases as a consequence of oxidative stress. Antioxid. Redox Signal. 8: 18071817.
27. Greene, V.,, H. Cao,, F. A. Schanne, and, D. C. Bartelt. 2002. Oxidative stress-induced calcium signalling in Aspergillus nidulans. Cell. Signal. 14: 437443.
28. Hamilton, A. J., and, M. D. Holdom. 1999. Antioxidant systems in the pathogenic fungi of man and their role in virulence. Med. Mycol. 37: 375389.
29. Heitman, J. 2005. Cell biology. A fungal Achilles’ heel. Science 309: 21752176.
30. Herranz, S.,, J. M. Rodriguez,, H. J. Bussink,, J. C. Sanchez-Ferrero,, H. N. Arst, Jr.,, M. A. Penalva, and, O. Vincent. 2005. Arrestin-related proteins mediate pH signaling in fungi. Proc. Natl. Acad. Sci. USA 102: 1214112146.
31. Hervás-Aguilar, A.,, J. M. Rodríguez,, J. Tilburn,, H. N. Arst, Jr., and, M. A. Peñalva. 2007. Evidence for the direct involvement of the proteasome in the proteolytic processing of the Aspergillus nidulans zinc finger transcription factor PacC. J. Biol. Chem. 282: 3473534747.
32. Ibrahim-Granet, O.,, B. Philippe,, H. Boleti,, E. Boisvieux-Ulrich,, D. Grenet,, M. Stern, and, J. P. Latgé. 2003. Phagocytosis and intracellular fate of Aspergillus fumigatus conidia in alveolar macrophages. Infect. Immun. 71: 891903.
33. Jahn, B.,, A. Koch,, A. Schmidt,, G. Wanner,, H. Gehringer,, S. Bhakdi, and, A. A. Brakhage. 1997. Isolation and characterization of a pigmentless-conidium mutant of Aspergillus fumigatus with altered conidial surface and reduced virulence. Infect. Immun. 65: 51105117.
34. Jahn, B.,, K. Langfelder,, U. Schneider,, C. Schindel, and, A. A. Brakhage. 2002. PKSP-dependent reduction of phagolysosome fusion and intracellular kill of Aspergillus fumigatus conidia by human monocyte-derived macrophages. Cell. Microbiol. 4: 793803.
35. Kraus, P. R., and, J. Heitman. 2003. Coping with stress: calmodulin and calcineurin in model and pathogenic fungi. Biochem. Biophys. Res. Commun. 311: 11511157.
36. Kupfahl, C.,, T. Heinekamp,, G. Geginat,, T. Ruppert,, A. Hartl,, H. Hof, and, A. A. Brakhage. 2006. Deletion of the gliP gene of Aspergillus fumigatus results in loss of gliotoxin production but has no effect on virulence of the fungus in a low-dose mouse infection model. Mol. Microbiol. 62: 292302.
37. Lamarre, C.,, O. Ibrahim-Granet,, C. Du,, R. Calderone, and, J. P. Latgé. 2007. Characterization of the SKN7 ortholog of Aspergillus fumigatus. Fungal Genet. Biol. 44: 682690.
38. Lehrer, R. I., and, M. J. Cline. 1969. Leukocyte myeloperoxidase deficiency and disseminated candidiasis: the role of myeloperoxidase in resistance to Candida infection. J. Clin. Investig. 48: 340345.
39. Lessing, F.,, O. Kniemeyer,, I. Wozniok,, J. Loeffler,, O. Kurzai,, A. Haertl, and, A. A. Brakhage. 2007. The Aspergillus fumigatus transcriptional regulator AfYap1 represents the major regulator for defense against reactive oxygen intermediates but is dispensable for pathogenicity in an intranasal mouse infection model. Eukaryot. Cell 6: 340345.
40. Levitz, S. M.,, M. E. Selsted,, T. Ganz,, R. I. Lehrer, and, R. D. Diamond. 1986. In vitro killing of spores and hyphae of Aspergillus fumigatus and Rhizopus oryzae by rabbit neutrophil cationic peptides and bronchoalveolar macrophages. J. Infect. Dis. 154: 340345.
41. Lundqvist-Gustafsson, H.,, M. Gustafsson, and, C. Dahlgren. 2000. Dynamic Ca2+ changes in neutrophil phagosomes: a source for intracellular Ca2+ during phagolysosome formation? Cell. Calcium 27: 340345.
42. Maubon, D.,, S. Park,, M. Tanguy,, M. Huerre,, C. Schmitt,, M. C. Prevost,, D. S. Perlin,, J. P. Latgé, and, A. Beauvais. 2006. AGS3, an a(1-3)glucan synthase gene family member of Aspergillus fumigatus, modulates mycelium growth in the lung of experientally infected mice. Fungal Genet. Biol. 43: 340345.
43. McDonagh, A.,, N. D. Fedorova,, J. Crabtree, J.,, Y. Yu,, S. Kim,, D. Chen,, O. Loss,, T. Cairns,, G. H. Goldman,, D. Armstrong-James,, K. Haynes,, H. Haas,, M. Schrettl,, G. May,, W. C. Nierman, and, E. Bignell. 2008. Subtelomere directed gene expression during initiation of invasive aspergillosis. PLoS Pathogens September.
44. Mittler, R. 2002. Oxidative stress, antioxidants and stress tolerance. Trends Plant Sci. 7: 340345.
45. Negrete-Urtasun, S.,, W. Reiter,, E. Diez,, S. H. Denison,, J. Tilburn,, E. A. Espeso,, M. A. Penalva, and, H. N. Arst, Jr. 1999. Ambient pH signal transduction in Aspergillus: completion of gene characterization. Mol. Microbiol. 33: 340345.
46. Newman, S. L.,, L. Gootee,, J. Hilty, and, R. E. Morris. 2006. Human macrophages do not require phagosome acidification to mediate fungistatic/fungicidal activity against Histoplasma capsulatum. J. Immunol. 176: 340345.
47. Paris, S.,, D. Wysong,, J. P. Debeaupuis,, K. Shibuya,, B. Philippe,, R. D. Diamond, and, J. P. Latgé. 2003. Catalases of Aspergillus fumigatus. Infect. Immun. 71: 340345.
48. Peñalva, M. A.,, J. Tilburn,, E. Bignell, and, H. N. Arst, Jr. 2008. Ambient pH gene regulation in fungi: making connections. Trends Microbiol. 16: 340345.
49. Perkhofer, S.,, C. Speth,, M. P. Dierich, and, C. Lass-Florl. 2007. In vitro determination of phagocytosis and intracellular killing of Aspergillus species by mononuclear phagocytes. Mycopathologia 163: 340345.
50. Philippe, B.,, O. Ibrahim-Granet,, M. C. Prevost,, M. A. Gougerot-Pocidalo,, M. Sanchez Perez,, A. Van der Meeren, and, J. P. Latgé. 2003. Killing of Aspergillus fumigatus by alveolar macrophages is mediated by reactive oxidant intermediates. Infect. Immun. 71: 340345.
51. Reeves, E. P.,, H. Lu,, H. L. Jacobs,, C. G. Messina,, S. Bolsover,, G. Gabella,, E. O. Potma,, A. Warley,, J. Roes, and, A. W. Segal. 2002. Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature 416: 340345.
52. Sbarra, A. J., and, M. L. Karnovsky. 1959. The biochemical basis of phagocytosis. I. Metabolic changes during the ingestion of particles by polymorphonuclear leukocytes. J. Biol. Chem. 234: 340345.
53. Schaffner, A.,, C. E. Davis,, T. Schaffner,, M. Markert,, H. Douglas, and, A. I. Braude. 1986. In vitro susceptibility of fungi to killing by neutrophil granulocytes discriminates between primary pathogenicity and opportunism. J. Clin. Investig. 78: 340345.
54. Schaffner, A.,, H. Douglas, and, A. Braude. 1982. Selective protection against conidia by mononuclear and against mycelia by polymorphonuclear phagocytes in resistance to Aspergillus. Observations on these two lines of defense in vivo and in vitro with human and mouse phagocytes. J. Clin. Investig. 69: 617631.
55. Sebghati, T. S.,, J. T. Engle, and, W. E. Goldman. 2000. Intracellular parasitism by Histoplasma capsulatum: fungal virulence and calcium dependence. Science 290: 13681372.
56. Segal, A. W.,, M. Geisow,, R. Garcia,, A. Harper, and, R. Miller. 1981. The respiratory burst of phagocytic cells is associated with a rise in vacuolar pH. Nature 290: 406409.
57. Segal, B. H.,, T. L. Leto,, J. I. Gallin,, H. L. Malech, and, S. M. Holland. 2000. Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore) 79: 170200.
58. Serrano, R. 1988. Structure and function of proton translocating ATP-ase in plasma membranes of plants and fungi. Biochim. Biophys. Acta 947: 128.
59. Sorensen, O. E. 1909. Enzymstudien. II: Mitteilung. Über die Messung und die Bedeutung der Wasserstoffionenkoncentration bei enzymatischen Prozessen. Biochem. Zeitsch. 1909: 131304.
60. Soriani, F. M.,, I. Malavazi,, M. E. da Silva Ferreira,, M. Savoldi,, M. R. Von Zeska Kress,, M. H. de Souza Goldman,, O. Loss,, E. Bignell, and, G. H. Goldman. 2008. Functional characterization of the Aspergillus fumigatus CRZ1 homologue, CrzA. Mol. Micro. 67: 12741291.
61. Soriani, F. M.,, V. P. Martins,, T. Magnani,, V. G. Tudella,, C. Curti, and, S. A. Uyemura. 2005. A PMR1-like calcium ATPase of Aspergillus fumigatus: cloning, identification and functional expression in S. cerevisiae. Yeast 22: 813824.
62. Spikes, S.,, R. Xu,, C. K. Nguyen,, G. Chamilos,, D. P. Kontoyiannis,, R. H. Jacobson,, D. E. Ejzykowicz,, L. Y. Chiang,, S. G. Filler, and, G. S. May. 2008. Gliotoxin production in Aspergillus fumigatus contributes to host-specific differences in virulence. J. Infect. Dis. 197: 479486.
63. Steinbach, W. J.,, R. A. Cramer, Jr.,, B. Z. Perfect,, Y. G. Asfaw,, T. C. Sauer,, L. K. Najvar,, W. R. Kirkpatrick,, T. F. Patterson,, D. K. Benjamin, Jr.,, J. Heitman, and, J. R. Perfect. 2006. Calcineurin controls growth, morphology, and pathogenicity in Aspergillus fumigatus. Eukaryot. Cell 5: 10911103.
64. Steinbach, W. J.,, J. L. Reedy,, R. A. Cramer, Jr.,, J. R. Perfect, and, J. Heitman. 2007. Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections. Nat. Rev. Microbiol. 5: 418430.
65. Takemoto, D.,, A. Tanaka, and, B. Scott. 2007. NADPH oxidases in fungi: diverse roles of reactive oxygen species in fungal cellular differentiation. Fungal Genet. Biol. 44: 10651076.
66. Tang, C. M.,, J. M. Smith,, H. N. Arst, Jr., and, D. W. Holden. 1994. Virulence studies of Aspergillus nidulans mutants requiring lysine or p-aminobenzoic acid in invasive pulmonary aspergillosis. Infect. Immun. 62: 52555260.
67. Tilburn, J.,, S. Sarkar,, D. A. Widdick,, E. A. Espeso,, M. Orejas,, J. Mungroo,, M. A. Penalva, and, H. N. Arst, Jr. 1995. The Aspergillus PacC zinc finger transcription factor mediates regulation of both acid- and alkaline-expressed genes by ambient pH. EMBO J. 14: 779790.
68. Tkalcevic, J.,, M. Novelli,, M. Phylactides,, J. P. Iredale,, A. W. Segal, and, J. Roes. 2000. Impaired immunity and enhanced resistance to endotoxin in the absence of neutrophil elastase and cathepsin G. Immunity 12: 201210.
69. Todd, R. B.,, M. A. Davis, and, M. J. Hynes. 2007. Genetic manipulation of Aspergillus nidulans: heterokaryons and diploids for dominance, complementation and haploidization analyses. Nat. Protoc. 2: 822830.
70. Vescovi, E. G.,, Y. Ayala,, E. A. Di Cera, and, E. A. Groisman. 1997. Characterisation of the bacterial sensor protein PhoQ. J. Biol. Chem. 272: 14401443.
71. Vincent, O.,, L. Rainbow,, J. Tilburn,, H. N. Arst, Jr., and, M. A. Penalva. 2003. YPXL/I is a protein interaction motif recognized by Aspergillus PalA and its human homologue, AIP1/Alix. Mol. Cell. Biol. 23: 16471655.
72. Waldorf, A. R.,, S. M. Levitz, and, R. D. Diamond. 1984. In vivo bronchoalveolar macrophage defense against Rhizopus oryzae and Aspergillus fumigatus. J. Infect. Dis. 150: 752760.
73. Williams, R. J. 2006. The evolution of calcium biochemistry. Biochim. Biophys. Acta 1763: 11391146.
74. Williams, R. L., and, S. Urbe. 2007. The emerging shape of the ESCRT machinery. Nat. Rev. Mol. Cell Biol. 8: 355368.
75. Wilsson, A.,, H. Lundqvist,, M. Gustafsson, and, O. Stendahl. 1996. Killing of phagocytosed Staphylococcus aureus by human neutrophils requires intracellular free calcium. J. Leukoc. Biol. 59: 902907.
76. Yu, B. P. 1994. Cellular defenses against damage from reactive oxygen species. Physiol. Rev. 74: 139162.

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