Activation of Macrophage Complement Receptors for Phagocytosis

  • Frank M. GriffinJr.
Part of the Contemporary Topics in Immunobiology book series (CTI, volume 13)


Engagement by immunoglobulin G (IgG) of Fc receptors of either polymorphonuclear or mononuclear phagocytes virtually always leads to ingestion of IgG-containing soluble and particulate complexes (Bianco et al., 1975; Ehlenberger and Nussenzweig, 1977; F. M. Griffin etal., 1975b, 1976; J. A. Griffin and Griffin, 1979; Mantovani, 1975; Mantovani et al., 1972;Quie et a1.,1968; Rabinovitch, 1967; Schreiber and Frank, 1972; Shaw and Griffin, 1981). Engagement of C3b receptors* by C3b contained in soluble immune complexes likewise results in ingestion of the complexes (Van Snick and Masson, 1978). A number of studies (Bar-Shavit et al., 1979; Diamond et al., 1973, 1974; Gigli and Nelson, 1968; Horwitz and Silverstein, 1980; Huber et al., 1968; Musson and Becker, 1977; Pearlman et al., 1969; Schreiber et al., 1982; Shurin and Stossel, 1978; Stossel et al., 1973) have demonstrated enhancement of phagocytosis of a variety of particles, chiefly microoraganisms, when they were coated with complement, even in the absence of immunoglobulin, and for many years it was assumed that ingestion of these microbes was mediated by the complement receptors of phagocytic cells. Several recent studies, however, have reported that engagement by particle-bound C3b of complement receptors of neutrophils, monocytes, and “resting” tissue macrophages, although always promoting efficient particle binding, fails to promote ingestion of C3b-coated particles (Bianco et al., 1975; Ehlenberger and Nussenzweig, 1977; F. M. Griffin, 1980,1981; F. M. Griffin et al.,1975a,b; F. M. Griffin and Griffin, 1980; J. A. Griffin and Griffin, 1979; Lay and Nussenzweig, 1968; Mantovani, 1975; Mantovani et al.,1972; Newman and Johnston, 1979; Scribner and Fahrney, 1976; Shaw and Griffin, 1981; Ward and Enders, 1933). Studies in rabbits (Brown et al., 1970) and guinea pigs Atkinson and Frank, 1974a,b; Schreiber and Frank, 1972) confirm the in vitro finding that macrophages are normally unable to phagocytize via their complement receptors. Erythrocytes coated with IgM, which became further coated with complement when injected intravenously, were rapidly cleared from these animals’ circulation by the liver. However, within a few minutes they reappeared in the bloodstream and circulated with a normal lifespan. Presumably these C3b-coated erythrocytes were bound via the C3b receptors of Kupffer cells but were released when C3b inactivator and proteases cleaved erythrocyte-bound C3b to C3 fragments not recognized by macrophages.


Complement Receptor Mouse Peritoneal Macrophage Receptor Mobility Thioglycollate Medium Soluble Immune Complex 
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  1. Atkinson, J. P., and Frank, M. M., 1974a, The effect of bacillus Calmette-Guérin-induced macrophage activation on the in vivo clearance of sensitized erythrocytes, J. Clin. Invest. 53: 1742–1749.PubMedCrossRefGoogle Scholar
  2. Atkinson, J. P., and Frank, M. M., 1974b, Studies on the in vivo effects of antibody. Interaction of IgM antibody and complement in the immune clearance and destruction of erythrocytes in man, J. Clin. Invest. 54: 339–348.PubMedCrossRefGoogle Scholar
  3. Axelrod, D., Ravdin, P., Koppel, D. F., Schlessinger, J., Webb, W. W., Elson, E. L., and Podleski, T. R., 1976, Lateral motion of fluorescently labeled acetylcholine, Proc. Natl. Acad, Sci. USA. 73: 2823–2827.CrossRefGoogle Scholar
  4. Bar-Shavit, Z., Raz, A., and Goldman, R., 1979, Complement and Fc receptor-mediated phagocytosis of normal and stimulated mouse peritoneal macrophages, Eur. J. Immunol. 9: 385–391.PubMedCrossRefGoogle Scholar
  5. Bianco, C., Griffin, F. M., Jr., and Silverstein, S. C., 1975, Studies of the macrophage complement receptor. Alteration of receptor function upon macrophage activation, J. Exp. Med. 141: 1278–1290.PubMedCrossRefGoogle Scholar
  6. Boxer, L. A., and Stossel, T. P., 1976, Interactions of actin, myosin, and an actin-binding protein of chronic myelogenous leukemia leukocytes, J. CTin. Invest. 57: 964–976.CrossRefGoogle Scholar
  7. Brown, D. L., Lachman, P. J., and Dacie, J. V., 1970, The in vivo behaviour of complement-coated red cells: Studies in C6-deficient, C3-depleted and normal rabbits, Clin. Exp. Immunol. 7: 401–422.PubMedGoogle Scholar
  8. Brown, E. J., Hosea, S. W., and Frank, M. M., 1980, Complement-mediated reticuloendothelial clearance in pneumococcal bacteremia, Fed. Proc. 39: 1204.Google Scholar
  9. Carlo, J. R., Ruddy, S., Studer, E. J., and Conrad, D. H., 1979, Complement receptor binding of C3b-coated cells treated with C3b inactivator, ß1H globulin and trypsin, J. Immunol. 123: 523–528.PubMedGoogle Scholar
  10. Diamond, R. D., May, J. E., Kane, M. A., Frank, M. M., and Bennett, J. E., 1973, The role of late complement components and the alternate complement pathway in experimental cryptococcosis, Proc. Soc. Exp. Biol. Med. 144: 312–315.PubMedGoogle Scholar
  11. Diamond, R. D., May, J. E., Kane, M. A., Frank, M. M., and Bennett, J. E., 1974, The role of the classical and alternate complement pathways in host defenses against Cryptococcus neoformans infection, J. Immunol. 122: 2260–2270.Google Scholar
  12. Dobson, N. J., Lambris, J. D., and Ross, G. D., 1981, Characteristics of isolated erythrocyte complement receptor type one (CR1, C4b-C3b receptor) and CR1-specific antibodies, J. Immunol. 126: 693–698.PubMedGoogle Scholar
  13. Douglas, S. D., 1976, Human monocyte spreading in vitro—inducers and effects on Fc and C3 receptors, Cell. Immunol. 21: 344–349.PubMedCrossRefGoogle Scholar
  14. Ehlenberger, A. G., and Nussenzweig, V., 1977, The role of membrane receptors for C3b and C3d in phagocytosis, J. Exp. Med. 145: 357–371.PubMedCrossRefGoogle Scholar
  15. Fearon, D. T., 1980, Identification of the membrane glycoprotein that is the C3b receptor of the human ertythrocyte, polymorphonuclear leukocyte, B lymphocyte, and monocyte, J. Exp. Med. 152: 20–30.PubMedCrossRefGoogle Scholar
  16. Fearon, D. T., Kameko, I., and Thompson, G. G., 1981, Membrane distribution and absorptive endocytosis by C3b receptors on human polymorphonuclear leukocytes, J. Exp. Med. 153: 1615–1628.PubMedCrossRefGoogle Scholar
  17. Frank, M. M., Hamburger, M. I., Lawley, T. J., Kimberly, R. P., and Plotz, P. H., 1979, Defective reticuloendothelial system Fc-receptor function in systemic lupus erythematosus, N. Engl. J. Med. 300: 518–523.PubMedCrossRefGoogle Scholar
  18. Gigli, I., and Nelson, R. A., 1968, Complement dependent immune phagocytosis. I. Requirements for C’1, C’4, C’2, C’3, Exp. Cell Res. 51: 45–67.PubMedCrossRefGoogle Scholar
  19. Griffin, F. M., Jr., 1980, Effects of soluble immune complexes on Fc receptor-and C3b receptor-mediated phagocytosis by macrophages, J. Exp. Med. 152: 905–919.PubMedCrossRefGoogle Scholar
  20. Griffin, F. M., Jr., 1981, Roles of macrophage Fc and C3b receptors in phagocytosis of immunologically coated Cryptococcus neoformans, Proc. Natl. Acad. Sci. USA 78: 3853–3857.PubMedCrossRefGoogle Scholar
  21. Griffin, F. M., Jr., and Griffin, J. A., 1980, Augmentation of macrophage complement receptor function in vitro. II. Characterization of the effects of a unique lymphokine upon the phagocytic capabilities of macrophages, J. Immunol. 125: 844–849.PubMedGoogle Scholar
  22. Griffin, F. M., Jr., and Mullinax, P. J., 1981, Augmentation of macrophage complement receptor function in vitro. III. C3b receptors that promote phagocytosis migrate within the plane of the macrophage plasma membrane, J. Exp. Med. 154: 291–305.PubMedCrossRefGoogle Scholar
  23. Griffin, F. M., Jr., Bianco, C., and Silverstein, S. C., 1975a, Characterization of the macrophage receptor for complement and demonstration of its functional independence from the receptor for the Fc portion of immunoglobulin G, J. Exp. Med. 141: 1269–1277.PubMedCrossRefGoogle Scholar
  24. Griffin, F. M., Jr., Griffin, J. A., Leiber, J. E., and Silverstein, S. C., 1975b, Studies on the mechanism of phagocytosis. I. Requirements for circumferential attachment of particlebound ligands to specific receptors on the macrophage plasma membrane, J. Exp. Med. 142: 1263–1282.PubMedCrossRefGoogle Scholar
  25. Griffin, F. M., Jr., Griffin, J. A., and Silverstein, S. C., 1976, Studies on the mechanism of phagocytosis. II. The interaction of macrophages with anti-immunoglobulin IgG-coated bone marrow-derived lymphocytes, J. Exp. Med. 144: 788–809.PubMedCrossRefGoogle Scholar
  26. Griffin, F. M., Jr., Luben, R. A., and Golde, D. W., 1984, A human lymphokine activates macrophage complement receptors for phagocytosis: studies using monoclonal anti-lymphokine antibodies, J. Leuk. Biol. (in press).Google Scholar
  27. Griffin, J. A., and Griffin, F. M., Jr., 1979, 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. 150: 653–675.PubMedCrossRefGoogle Scholar
  28. Haakenstad, A. O., and Mannik, M., 1974, Saturation of the reticuloendothelial system with soluble immune complexes, J. Immunol. 112: 1939–1948.PubMedGoogle Scholar
  29. Hallgren, R., Hakanssen, L., and Venge, P., 1978, Kinetic studies of phagocytosis. I. The serum independent particle uptake of PMN from patients with rheumatoid arthritis and systemic lupus erythematosus, Arthritis Rheum. 21: 107–113.PubMedCrossRefGoogle Scholar
  30. Hartwig, J. H., and Stossel, T. P., 1975, Isolation and properties of actin, myosin, and a new actin-binding protein in rabbit alveolar macrophages, J. Biol. Chem. 250: 5696–5705.PubMedGoogle Scholar
  31. Horwitz, M. A., and Silverstein, S. C., 1980, Influence of the Escherichia coli capsule on complement fixation and on phagocytosis and killing by human phagocytes, J. Clin. Invest. 65: 82–94.PubMedCrossRefGoogle Scholar
  32. Huber, H., Polley, M. J., Linscott, W. D., Fudenberg, H. H., and Muller-Eberhard, H. J., 1968, Human monocytes: Distinct receptor sites for the third component of complement and for immunoglobulin G, Science 162: 1281–1283.PubMedCrossRefGoogle Scholar
  33. Kaplan, G., Eskeland, T., and Seljelid, R., 1978, Difference in the effect of immobilized ligands on the Fc and C3 receptors of mouse peritoneal macrophages in vitro, Scand. J. Immunol. 7: 19–24.PubMedCrossRefGoogle Scholar
  34. Lambris, J. D., and Ross, G. D., 1982, Assay of membrane complement receptors (CR1 and CR2) with C3b-and C3d-coated fluorescent microspheres, J. Immunol. 128:186–189. Lay, W. H., and Nussenzweig, V., 1968, Receptors for complement on leukocytes, J. Exp.Med. 128: 991–1009.Google Scholar
  35. Mantovani, B., 1975, Different roles of IgG and complement receptors in phagocytosis by polymorphonuclear leukocytes, J. Immunol. 115: 15–17.PubMedGoogle Scholar
  36. Mantovani, B., 1981, Phagocytosis of immune complexes mediated by IgM and C3 receptors by macrophages from mice treated with glycogen, J. Immunol. 126: 127–130.PubMedGoogle Scholar
  37. Mantovani, B., Rabinovitch, M., and Nussenzweig, V., 1972, Phagocytosis of immune complexes by macrophages. Different roles of the macrophage receptor sites for complement (C3) and for immunoglobulin (IgG), J. Exp. Med. 135: 780–792.PubMedCrossRefGoogle Scholar
  38. Michl, J., Pieczonka, M. M., Unkeless, J. C., and Silverstein, S. C., 1979, Effects of immobilized immune complexes on Fc-and complement-receptor function in resident and thioglycollate-elicited mouse peritoneal macrophages, J. Exp. Med. 150: 607–621.PubMedCrossRefGoogle Scholar
  39. Musson, R. A., and Becker, E. L., 1977, The role of an activatable esterase in immune-dependent phagocytosis by human neutrophils, J. Immunol. 118: 1354–1365.PubMedGoogle Scholar
  40. Newman, S. L., and Johnston, R. B., Jr., 1979, Role of binding through C3b and IgG in polymorphonuclear neutrophil function: Studies with trypsin-generated C3b, J. Immunol. 123: 1839–1846.PubMedGoogle Scholar
  41. Newman, S. L., Musson, R. A., and Henson, P. M., 1980, Development of functional complement receptors during in vitro maturation of human monocytes into macrophages, J. Immunol. 125: 2236–2244.PubMedGoogle Scholar
  42. Nogueira, N., Gordon, S., and Cohn, Z., 1977, Trypanosoma cruzi: Modification of macrophage function during infection, J. Exp. Med. 146: 157–171.Google Scholar
  43. Nowakowski, N., Edelson, P. J., and Bianco, C., 1980, Activation of C3H/HeJ macrophages by endotoxin, J. Immunol. 125: 2189–2194.PubMedGoogle Scholar
  44. Pearlman, D. S., Ward, P. A., and Becker, E. L., 1969, The requirement of serine esterase function in complement-dependent erythrophagocytosis, J. Exp. Med. 130: 745–764.PubMedCrossRefGoogle Scholar
  45. Petty, H. R., Smith, L. M., Fearon, D. T., and McConnell, H. M., 1980, Lateral distribution and diffusion of the C3b receptor of complement, HLA antigens, and lipid probes in peripheral blood leukocytes, Proc. Natl. Acad. Sci. USA 77: 6587–6591.PubMedCrossRefGoogle Scholar
  46. Quie, P. G., Messner, R. P., and Williams, R. C., 1968, Phagoctyosis in subacute bacterial endocarditis. Localization of the primary opsonic site to Fc fragment, J. Exp. Med. 128: 553–570.PubMedCrossRefGoogle Scholar
  47. Rabellino, E. M., Ross, G. D., and Polley, M. J., 1978, Membrane receptors of mouse leukocytes. I. Two types of complement receptors for different regions of C3, J. Immunol. 120: 879–885.PubMedGoogle Scholar
  48. Rabinovitch, M., 1967, Studies on the immunoglobulins which stimulate the ingestion of glutaraldehyde-treated red cells attached to macrophages, J. Immunol. 99: 1115–1120.PubMedGoogle Scholar
  49. Rabinovitch, M., Manejias, R. E., and Nussenzweig, V., 1975, Selective phagocytic paralysis induced by immobilized immune complexes, J. Exp. Med. 142: 827–838.PubMedCrossRefGoogle Scholar
  50. Ragsdale, C. G., and Arend, W. P., 1980, Loss of Fc receptor activity after culture of human monocytes on surface-bound immune complexes. Mediation by cyclic nucleotides, J. Exp. Med. 151: 32–44.PubMedCrossRefGoogle Scholar
  51. Ross, G. D., and Rabellino, E. M., 1979, Identification of a neutrophil and monocyte complement receptor (CR3) that is distinct from lymphocyte CRI and CR2 and specific for a site contained within C3bi, Fed. Proc. 38: 1467.Google Scholar
  52. Ross, G. D., Lambris, J. D., Cain, J. A., and Newman, S. L., 1982, Generation of three different fragments of bound C3 with purified Factor I or serum. I. Requirements for Factor H vs CR1 cofactor activity, J. Immunol. 129: 2051–2060.PubMedGoogle Scholar
  53. Schlessinger, J., Barak, L. S., Yamada, K. M., Pastan, I., and Webb, W. W., 1977, Mobility and distribution of a cell surface glycoprotein and its interaction with other membrane components, Proc. Natl. Acad. Sci. USA 74: 2909–2913.PubMedCrossRefGoogle Scholar
  54. Schmitt, M., Mussel, H.-H., and Dierich, M. P., 1981, Qualitative and quantitative assessment of C3-receptor reactivities on lymphoid and phagocytic cell, J. Immunol. 126: 2042–2047.PubMedGoogle Scholar
  55. Schreiber, A. D., and Frank, M. M., 1972, Role of antibody and complement in the immune clearance and destruction of erythrocytes. I. In vivo effects of IgG and IgM complement-fixing sites, J. Clin. Invest. 51: 575–582.Google Scholar
  56. Schreiber, R. D., Pangburn, M. K., Bjornson, A. B., Brothers, M. A., and Muller-Eberhard, H. J., 1982, The role of C3 fragments in endocytosisand extracellularcytotoxic reactions by polymorphonuclear leukocytes, Clin. Immunol. Immunopathol. 23: 335–357.PubMedCrossRefGoogle Scholar
  57. Schribner, D. J., and Fahrney, D., 1976, Neutrophil receptors for IgG and complement: Their roles in the attachment and ingestion phases of phagocytosis, J. Immunol. 116: 892–897.Google Scholar
  58. Shaw, D. R., and Griffin, F. M., Jr., 1981, Phagocytosis requires repeated triggering of macrophage phagocytic receptors during particle ingestion, Nature 289: 409–411.PubMedCrossRefGoogle Scholar
  59. Shaw, D. R. and Griffin, F. M., Jr., 1982, Thioglycollate-elicited mouse peritoneal macrohages are less efficient than resident macrophages in anitbody-dependent cell-mediated cytolysis, J. Immunol. 128: 433–440.PubMedGoogle Scholar
  60. Shurin, S. B., and Stossel, T. P., 1978, Complement (C3)-activated phagocytosis by lung macrophages, J. Immunol. 120: 1305–1312.PubMedGoogle Scholar
  61. Stossel, T. P., 1977, Contractile proteins in phagocytosis: An example of cell surface-tocytoplasm communication, Fed. Proc. 36: 2181–2184.PubMedGoogle Scholar
  62. Stossel, T. P., and Hartwig, J. H., 1975, Interactions between actin, myosin, and a new actin-binding protein of rabbit alveolar macrophages. Macrophage myosin Mgt+-adenosine triphosphatase requires a cofactor for activation by actin, J. Biol. Chem. 250: 5706–5712.PubMedGoogle Scholar
  63. Stossel, T. P., and Hartwig, J. H., 1976, Interactions of actin, myosin, and a new actin-binding protein of rabbit pulmonary macrophages. II. Role in cytoplasmic movement and phagocytosis, J. Cell Biol. 68: 602–619.PubMedCrossRefGoogle Scholar
  64. Stossel, T. P., Alper, C. A., and Rosen, F. S., 1973, Serum-dependent phagocytosis of paraffin oil emulsified with bacterial Iipopolysaccharide, J. Exp. Med. 137: 690–705.PubMedCrossRefGoogle Scholar
  65. Tabor, D. R., and Saluk, P. H., 1981, The functional heterogeneity of murine-resident macrophages to a chemotactic signal and induction of C3b-receptor-mediated ingestion, Immunol. Lett. 3: 371–376.PubMedCrossRefGoogle Scholar
  66. Van Snick, J. L., and Masson, P. L., 1978, The effect of complement on the ingestion of soluble antigen-antibody complexes and IgM aggregates by mouse peritoneal macrophages, J. Exp. Med. 148: 903–914.PubMedCrossRefGoogle Scholar
  67. Ward, H. K., and Enders, J. F., 1933, An analysis of the opsonic and tropic action of normal and immune sera based on experiments with the pneumococcus, J. Exp. Med. 57: 527547.Google Scholar
  68. Wellek, B., Hahn, H. H., and Opferkuch, W., 1975, Evidence for macrophage C3d-receptor active in phagocytosis, J. Immunol. 114: 1643–1645.PubMedGoogle Scholar
  69. Wright, S. D., and Silverstein, S. C., 1982, Tumor-promoting phorbol esters stimulate C3b and C3b’ receptor-mediated phagocytosis in cultured human monocytes, J. Exp. Med. 156: 1149–1164.PubMedCrossRefGoogle Scholar
  70. Wrigley, D. M., and Saluk, P. H., 1981, Induction of C3b-mediated phagocytosis in macrophages by distinct populations of lipopolysaccharide-stimulated lymphocytes, Infect. Immun. 34: 780–786.PubMedGoogle Scholar
  71. Yin, H. L., and Stossel, T. P., 1979, Control of cytosplasmic actin gel-sol transformation by gelsolin, a calcium-dependent regulatory protein, Nature 281: 583–586.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • Frank M. GriffinJr.
    • 1
  1. 1.Division of Infectious Diseases Department of MedicineUniversity of Alabama in BirminghamBirminghamUSA

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