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. 1988 Oct;82(4):1192–1201. doi: 10.1172/JCI113716

Studies on the molecular mechanisms of human Fc receptor-mediated phagocytosis. Amplification of ingestion is dependent on the generation of reactive oxygen metabolites and is deficient in polymorphonuclear leukocytes from patients with chronic granulomatous disease.

H D Gresham 1, J A McGarr 1, P G Shackelford 1, E J Brown 1
PMCID: PMC442669  PMID: 3049672

Abstract

Human PMN and monocytes both possess a mechanism for amplifying Fc receptor-mediated phagocytic function, which is dependent on activation of the respiratory burst. The pathway for augmentation of phagocytosis requires superoxide anion, hydrogen peroxide, and lactoferrin and is independent of the hydrogen peroxide-MPO-halide system. In neither cell type is this mechanism induced upon exposure to the opsonized target. PMN require an additional signal for stimulation of the respiratory burst; this is not true of monocytes. On the other hand, monocytes require an exogenous source of lactoferrin in order to activate this pathway for enhanced ingestion. The dependence of this pathway for both PMN and monocytes on superoxide anion, hydrogen peroxide, and cell-bound lactoferrin is consistent with a role for locally generated reactive oxygen metabolites, possibly hydroxyl radicals, in phagocytosis amplification. Patients with chronic granulomatous disease, who are genetically deficient in the ability to activate the respiratory burst, are unable to amplify Fc receptor-mediated phagocytosis. Thus, these patients may have a previously unrecognized defect in the recruitment of phagocytic function at inflammatory sites.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ambruso D. R., Johnston R. B., Jr Lactoferrin enhances hydroxyl radical production by human neutrophils, neutrophil particulate fractions, and an enzymatic generating system. J Clin Invest. 1981 Feb;67(2):352–360. doi: 10.1172/JCI110042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Babior B. M. Oxygen-dependent microbial killing by phagocytes (second of two parts). N Engl J Med. 1978 Mar 30;298(13):721–725. doi: 10.1056/NEJM197803302981305. [DOI] [PubMed] [Google Scholar]
  3. Baehner R. L., Karnovsky M. J., Karnovsky M. L. Degranulation of leukocytes in chronic granulomatous disease. J Clin Invest. 1969 Jan;48(1):187–192. doi: 10.1172/JCI105967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Birgens H. S., Hansen N. E., Karle H., Kristensen L. O. Receptor binding of lactoferrin by human monocytes. Br J Haematol. 1983 Jul;54(3):383–391. doi: 10.1111/j.1365-2141.1983.tb02113.x. [DOI] [PubMed] [Google Scholar]
  5. Bohnsack J. F., Kleinman H. K., Takahashi T., O'Shea J. J., Brown E. J. Connective tissue proteins and phagocytic cell function. Laminin enhances complement and Fc-mediated phagocytosis by cultured human macrophages. J Exp Med. 1985 May 1;161(5):912–923. doi: 10.1084/jem.161.5.912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Boxer L. A., Haak R. A., Yang H. H., Wolach J. B., Whitcomb J. A., Butterick C. J., Baehner R. L. Membrane-bound lactoferrin alters the surface properties of polymorphonuclear leukocytes. J Clin Invest. 1982 Nov;70(5):1049–1057. doi: 10.1172/JCI110692. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Britigan B. E., Rosen G. M., Chai Y., Cohen M. S. Do human neutrophils make hydroxyl radical? Determination of free radicals generated by human neutrophils activated with a soluble or particulate stimulus using electron paramagnetic resonance spectrometry. J Biol Chem. 1986 Apr 5;261(10):4426–4431. [PubMed] [Google Scholar]
  8. Britigan B. E., Rosen G. M., Thompson B. Y., Chai Y., Cohen M. S. Stimulated human neutrophils limit iron-catalyzed hydroxyl radical formation as detected by spin-trapping techniques. J Biol Chem. 1986 Dec 25;261(36):17026–17032. [PubMed] [Google Scholar]
  9. Broxmeyer H. E., DeSousa M., Smithyman A., Ralph P., Hamilton J., Kurland J. I., Bognacki J. Specificity and modulation of the action of lactoferrin, a negative feedback regulator of myelopoiesis. Blood. 1980 Feb;55(2):324–333. [PubMed] [Google Scholar]
  10. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  11. Ehlenberger A. G., Nussenzweig V. The role of membrane receptors for C3b and C3d in phagocytosis. J Exp Med. 1977 Feb 1;145(2):357–371. doi: 10.1084/jem.145.2.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fleit H. B., Wright S. D., Durie C. J., Valinsky J. E., Unkeless J. C. Ontogeny of Fc receptors and complement receptor (CR3) during human myeloid differentiation. J Clin Invest. 1984 Feb;73(2):516–525. doi: 10.1172/JCI111238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gaither T. A., Medley S. R., Gallin J. I., Frank M. M. Studies of phagocytosis in chronic granulomatous disease. Inflammation. 1987 Jun;11(2):211–227. doi: 10.1007/BF00916022. [DOI] [PubMed] [Google Scholar]
  14. Gresham H. D., Clement L. T., Lehmeyer J. E., Griffin F. M., Jr, Volanakis J. E. Stimulation of human neutrophil Fc receptor-mediated phagocytosis by a low molecular weight cytokine. J Immunol. 1986 Aug 1;137(3):868–875. [PubMed] [Google Scholar]
  15. Gresham H. D., Clement L. T., Volanakis J. E., Brown E. J. Cholera toxin and pertussis toxin regulate the Fc receptor-mediated phagocytic response of human neutrophils in a manner analogous to regulation by monoclonal antibody 1C2. J Immunol. 1987 Dec 15;139(12):4159–4166. [PubMed] [Google Scholar]
  16. Griffin J. A., Griffin F. M., Jr Augmentation of macrophage complement receptor function in vitro. I. Characterization of the cellular interactions required for the generation of a T-lymphocyte product that enhances macrophage complement receptor function. J Exp Med. 1979 Sep 19;150(3):653–675. doi: 10.1084/jem.150.3.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hohn D. C., Lehrer R. I. NADPH oxidase deficiency in X-linked chronic granulomatous disease. J Clin Invest. 1975 Apr;55(4):707–713. doi: 10.1172/JCI107980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Johnston R. B., Jr, Keele B. B., Jr, Misra H. P., Lehmeyer J. E., Webb L. S., Baehner R. L., RaJagopalan K. V. The role of superoxide anion generation in phagocytic bactericidal activity. Studies with normal and chronic granulomatous disease leukocytes. J Clin Invest. 1975 Jun;55(6):1357–1372. doi: 10.1172/JCI108055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Johnston R. B., Jr, Lehmeyer J. E., Guthrie L. A. Generation of superoxide anion and chemiluminescence by human monocytes during phagocytosis and on contact with surface-bound immunoglobulin G. J Exp Med. 1976 Jun 1;143(6):1551–1556. doi: 10.1084/jem.143.6.1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Klebanoff S. J., Vadas M. A., Harlan J. M., Sparks L. H., Gamble J. R., Agosti J. M., Waltersdorph A. M. Stimulation of neutrophils by tumor necrosis factor. J Immunol. 1986 Jun 1;136(11):4220–4225. [PubMed] [Google Scholar]
  21. Korchak H. M., Vienne K., Rutherford L. E., Wilkenfeld C., Finkelstein M. C., Weissmann G. Stimulus response coupling in the human neutrophil. II. Temporal analysis of changes in cytosolic calcium and calcium efflux. J Biol Chem. 1984 Apr 10;259(7):4076–4082. [PubMed] [Google Scholar]
  22. Kurlander R. J., Batker J. The binding of human immunoglobulin G1 monomer and small, covalently cross-linked polymers of immunoglobulin G1 to human peripheral blood monocytes and polymorphonuclear leukocytes. J Clin Invest. 1982 Jan;69(1):1–8. doi: 10.1172/JCI110419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Levy P. C., Shaw G. M., LoBuglio A. F. Human monocyte, lymphocyte, and granulocyte antibody-dependent cell-mediated cytotoxicity toward tumor cells. I. General characteristics of cytolysis. J Immunol. 1979 Aug;123(2):594–599. [PubMed] [Google Scholar]
  24. Messner R. P., Jelinek J. Receptors for human gamma G globulin on human neutrophils. J Clin Invest. 1970 Dec;49(12):2165–2171. doi: 10.1172/JCI106435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. O'Brien P. J. Superoxide production. Methods Enzymol. 1984;105:370–378. doi: 10.1016/s0076-6879(84)05050-3. [DOI] [PubMed] [Google Scholar]
  26. Perussia B., Kobayashi M., Rossi M. E., Anegon I., Trinchieri G. Immune interferon enhances functional properties of human granulocytes: role of Fc receptors and effect of lymphotoxin, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor. J Immunol. 1987 Feb 1;138(3):765–774. [PubMed] [Google Scholar]
  27. Pommier C. G., Inada S., Fries L. F., Takahashi T., Frank M. M., Brown E. J. Plasma fibronectin enhances phagocytosis of opsonized particles by human peripheral blood monocytes. J Exp Med. 1983 Jun 1;157(6):1844–1854. doi: 10.1084/jem.157.6.1844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pryzwansky K. B., MacRae E. K., Spitznagel J. K., Cooney M. H. Early degranulation of human neutrophils: immunocytochemical studies of surface and intracellular phagocytic events. Cell. 1979 Dec;18(4):1025–1033. doi: 10.1016/0092-8674(79)90215-0. [DOI] [PubMed] [Google Scholar]
  29. Root R. K., Metcalf J. A. H2O2 release from human granulocytes during phagocytosis. Relationship to superoxide anion formation and cellular catabolism of H2O2: studies with normal and cytochalasin B-treated cells. J Clin Invest. 1977 Dec;60(6):1266–1279. doi: 10.1172/JCI108886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sokol-Anderson M. L., Brajtburg J., Medoff G. Amphotericin B-induced oxidative damage and killing of Candida albicans. J Infect Dis. 1986 Jul;154(1):76–83. doi: 10.1093/infdis/154.1.76. [DOI] [PubMed] [Google Scholar]
  31. Stendahl O., Coble B. I., Dahlgren C., Hed J., Molin L. Myeloperoxidase modulates the phagocytic activity of polymorphonuclear neutrophil leukocytes. Studies with cells from a myeloperoxidase-deficient patient. J Clin Invest. 1984 Feb;73(2):366–373. doi: 10.1172/JCI111221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Stossel T. P., Root R. K., Vaughan M. Phagocytosis in chronic granulomatous disease and the Chediak-Higashi syndrome. N Engl J Med. 1972 Jan 20;286(3):120–123. doi: 10.1056/NEJM197201202860302. [DOI] [PubMed] [Google Scholar]
  33. Tritsch G. L., Niswander P. W. Purine salvage pathway enzyme activity in tuftsin-stimulated macrophages. Ann N Y Acad Sci. 1983;419:87–92. doi: 10.1111/j.1749-6632.1983.tb37094.x. [DOI] [PubMed] [Google Scholar]
  34. Wright S. D., Silverstein S. C. Tumor-promoting phorbol esters stimulate C3b and C3b' receptor-mediated phagocytosis in cultured human monocytes. J Exp Med. 1982 Oct 1;156(4):1149–1164. doi: 10.1084/jem.156.4.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]

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