Structure and Modulation of Fc and Complement Receptors

  • Jay C. Unkeless
  • Samuel D. Wright
Part of the Contemporary Topics in Immunobiology book series (CTI, volume 14)


A striking feature of the professional phagocytes first observed by Metchnikoff (1887) is their ability to bind and ingest foreign particles. In carrying out this vital task, the polymorphonuclear leukocyte (PMN) or macrophage must first recognize the intruder. The mechanism by which cells accomplish this recognition is, for many particles such as Latex or carbon, not well understood, and may not proceed through interaction of the particle with a receptor. On the other hand, many highly dangerous particles, such as bacteria and yeast, are recognized with the aid of opsonins—proteins that bind specifically to the intruder as a signal for phagocytosis (Griffin, 1977). Ingestion of these opsonin-coated particles is triggered by interaction with specific glycoprotein receptors on the cell plasma membrane. This chapter addresses exclusively receptor-mediated phagocytosis.


Complement Receptor J774 Cell Mouse Macrophage Cell Line Human Monocyte Cell Line C3bi Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anderson, C. L., 1982, isolation of the receptor for IgG from a human monocyte cell line (U937) and from human peripheral blood monocytes, J. Exp. Med. 156:1794.PubMedCrossRefGoogle Scholar
  2. Anderson, C. L., and Grey, H. M., 1978, Physicochemical separation of two distinct Fc receptors on murine macrophage-like cell lines, J. Immunol. 121:648.PubMedGoogle Scholar
  3. Anderson, C. L., and Spiegelberg, H. L., 1981, Macrophage receptors for IgE: binding of IgE to specific IgE receptors on a human macrophage cell line U 937, J. Immunol. 126:2470.PubMedGoogle Scholar
  4. Azline, S. G., and Reaven, E. P., 1974, Inhibition of phagocytosis and plasma membrane mobility of the cultivated macrophage by cytochalasin b. Role of subplasmalemmal microfilaments, J. Cell Biol. 62:647.CrossRefGoogle Scholar
  5. Bar-Shavit, Z., Goldman, R., Stabinsky, Y., Gottlieb, P., Fridkin, M., Teichberg, V. I., and Blumberg, S., 1980, Enhancement of phagocytosis—a newly found activity of Substance P residing in its N-terminal tetrapeptide sequence, Biochem. Biophys. Res. Commun. 94:1445.PubMedCrossRefGoogle Scholar
  6. Beller, D. I., Springer, T. A., and Schreiber, R. D., 1982, Anti-Mac-1 selectively inhibits the mouse and human type three complement receptor, J. Exp. Med. 156:1000.PubMedCrossRefGoogle Scholar
  7. Berken, A., and Benacerraf, B., 1966, Properties of antibodies cytophilic for macrophages, J. Exp. Med. 123:119.PubMedCrossRefGoogle Scholar
  8. Bianco, C., Griffin, F. M., and Silverstein, S. C., 1975, Studies of the macrophage complement receptor. Alteration of receptor function upon macrophage activation. J. Exp. Med. 141:1278.PubMedCrossRefGoogle Scholar
  9. Boltz-Nitulescu, G., Bazin, H., and Spiegelberg, H. L., 1981, Specificity of Fc receptors for IgG2a, IgGl/IgG2b, and IgE in rat macrophages, J. Exp. Med. 154:374.PubMedCrossRefGoogle Scholar
  10. Capron, A., Dessaint, J.-P., Capron, M., and Bazin, H., 1975, Specific IgE antibodies in immune adherence of normal macrophages to Schistosoma mansoni schistosomules, Nature 253:747.CrossRefGoogle Scholar
  11. Carlo, J. R., Ruddy, S., Studer, E. J., and Conrad, D. H., 1979, Complement receptor binding of C3b-coated cells treated with C3b inactivator, beta 1H globulin and trypsin, J. Immunol. 123:523.PubMedGoogle Scholar
  12. Davignon, D., Martz, E., Reynolds, T., Kurzinger, K., and Springer, T. A., 1981, Lymphocyte function-associated antigen 1 (LFA-1): A surface antigen distinct from Lyt-2,3 that participates in T lymphocyte-mediated killing, Proc. Natl. Acad. Sci. (USA) 78: 4535.CrossRefGoogle Scholar
  13. Day, N. K., Moncada, B., and Good, R. A., 1977, Inherited deficiencies of the complement system, in: Comprehensive Immunology, Vol. 2: Biological Amplification Systems in Immunology (N. K. Day and R. A. Good, eds.), pp. 229–245, Plenum, New York.Google Scholar
  14. Diamond, B., and Scharff, M. D., 1980, IgG1 and IgG2b share the Fc receptor on mouse macrophages, J. Immunol. 125: 631.PubMedGoogle Scholar
  15. Diamond, B., and Yelton, D. E., 1981, A new Fc receptor on mouse macrophages binding IgG3, J. Exp. Med. 153:514.PubMedCrossRefGoogle Scholar
  16. Diamond, B., Bloom, E. R., and Scharff, M. D., 1978, The Fc receptors of primary and cultured phagocytic cells studied with homogeneous antibodies, J. Immunol. 121:1978.Google Scholar
  17. Dickler, H. B., 1976, Lymphocyte receptors for immunoglobulin, Adv. Immunol. 24: 167.PubMedCrossRefGoogle Scholar
  18. Ehlenberger, A. G., and Nussenzweig, V., 1977, The role of membrane receptors for C3b and C3d in phagocytosis, J. Exp. Med. 145: 357.PubMedCrossRefGoogle Scholar
  19. Fanger, M. W., Shen, L., Pugh, J., and Bernier, G. M., 1980, Subpopulations of human peripheral granulocytes and monocytes express receptors for IgA, Proc. Natl. Acad. Sci. (USA) 77: 3640.CrossRefGoogle Scholar
  20. Fearon, D. T., 1980, Identification of the membrane glycoprotein that is the C3b receptor of the human erythrocyte, polymorphonuclear leukocyte, and monocyte, J. Exp. Med. 152: 20.PubMedCrossRefGoogle Scholar
  21. Fearon, D. T., Kaneko, I., and Thomson, G. G., 1981, Membrane distribution and adsorptive endocytosis by C3b receptors on human polymorphonuclear leukocytes, J. Exp. Med. 153:1615.PubMedCrossRefGoogle Scholar
  22. Fleit, H. B., Wright, S. D., and Unkeless, J. C., 1982, Human neutrophil Fc receptor distribution and structure, Proc. Natl. Acad. Sci. (USA) 79: 3275.CrossRefGoogle Scholar
  23. Frank, M. M., moderator, Lawley, T. J., Hamburger, M.I., and Brown, E. J., discussants, 1983, Immunoglobulin G Fc receptor-mediated clearance in autoimmune diseases, Ann. Intern. Med. 98: 206.PubMedGoogle Scholar
  24. Gebel, H., Hoover, R. G., and Lynch, R. G., 1979, Lymphocyte surface membrane immunoglobulin in myeloma. I. M315-bearing T lymphocytes in mice with MOPC-315, J. Immunol. 123:1110.PubMedGoogle Scholar
  25. Gonzalez-Molina, A., and Spiegelberg, H. L., 1978, A subpopulation of normal human periphaeral B lymphocytes that bind IgE, J. Clin. Invest. 59: 616.CrossRefGoogle Scholar
  26. Griffin, F. M., Jr., 1977, Opsonization, in: Comprehensive Immunology, Vol. 2: Biological Amplification Systems in Immunology (N. K. Day and R. A. Good, eds.), pp. 85–113, Plenum, New York.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.PubMedCrossRefGoogle Scholar
  28. 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 membrane, J. Exp. Med. 154: 291.PubMedCrossRefGoogle Scholar
  29. Griffin, F. M., Jr., and Silverstein, S. C., 1974, Segmental response of the macrophage plasma membrane to a phagocytic stimulus, J. Exp. Med. 139: 323.PubMedCrossRefGoogle Scholar
  30. Griffin, F. M., Jr., Griffin, J. A., Leider, J. E., and Silverstein, S. C., 1975, Studies on the mechanism of phagocytosis. I. Requirements for circumferential attachment of particlebound ligands to specific receptors of the macrophage plasma membrane. J. Exp. Med. 142: 1263.PubMedCrossRefGoogle Scholar
  31. Guyre, P. M., Crabtree, G. R., Bodwell, J. E., and Munck, A., 1981, MLC-conditioned media stimulate an increase in Fc receptors on human macrophages, J. Immunol. 126: 666.PubMedGoogle Scholar
  32. Guyre, P. M., Morganelli, P. M., and Miller, R., 1983, Recombinant immune interferon increases IgG Fc receptors on cultured human mononuclear phagocytes, J. Clin. Invest. 72: 393.PubMedCrossRefGoogle Scholar
  33. Haeffner-Cavaillon, N., Klein, M., and Dorrington, K. J., 1979, Studies on the Fc gamma receptor of the murine macrophage-like cell line P388D1. I. The binding of homologous and heterologous immunoglobulin G, J. Immunol. 123:1905.PubMedGoogle Scholar
  34. Hamburg, S. I., Fleit, H. B., Unkeless, J. C., and Rabinovitch, M., 1980, Mononuclear phagocytes: Responders to and producers of interferon, Ann. NY Acad. Sci. 350: 72.PubMedCrossRefGoogle Scholar
  35. Holowka, D., and Metzger, H., 1982, Further characterization of the B-component of the receptor for immunoglobulin E, Mol. Immunol. 19: 219.CrossRefGoogle Scholar
  36. Holowka, D., Hartmann, H., Kanellopoulos, J., and Metzger, H., 1980, Association of the receptor for immunoglobulin E with an endogenous polypeptide in rat basophilic leukemia cells, J. Recept. Res. 1:41.PubMedGoogle Scholar
  37. Hoover, R. G., and Lynch, R. G., 1980, Lymphocyte surface membrane immunoglobulin in myeloma II. T cells with IgA-Fc receptors are markedly increased in mice with IgA plasmacytomas, J. Immunol. 125: 1280.PubMedGoogle Scholar
  38. Iida, K., and Nussenzweig, V., 1981, Complement receptor is an inhibitor of the complement cascade, J. Exp. Med. 153:1138.PubMedCrossRefGoogle Scholar
  39. Kanellopoulos, J., Rossi, G., and Metzger, H., 1979, Preparative isolation of the cell receptor for immunoglobulin E, J. Biol. Chem. 254: 7691.PubMedGoogle Scholar
  40. Kaplan, G., 1977, Differences in the mode of phagocytosis with Fc and C3 receptors in macrophages, Scand. J. Immunol. 6: 797.PubMedCrossRefGoogle Scholar
  41. Kurlander, R. J., and Batker, J., 1982, The binding of human immunoglobulin G1 monomer and small cross-linked polymers of immunoglobulin G1 to human peripheral blood monocytes and polymorphonuclear leukocytes, J. Clin. Invest. 69: 1.PubMedCrossRefGoogle Scholar
  42. Langlois, A. J., Matthews, T., Roloson, G. J., Thiel, H.-J., Collins, J. J., and Bolognesi, D. P., 1981, Immunologic control of the ascites form of murine adenocarcinoma 755. V. Antibody-directed macrophages mediate tumor cell destruction, J. Immunol. 126: 2337.PubMedGoogle Scholar
  43. Lane, B. C., and Cooper, S. M., 1982, Fc receptors of mouse cell lines. I. Distinct proteins mediate the IgG subclass-specific Fc binding activities of macrophages, J. Immunol. 128: 1819.PubMedGoogle Scholar
  44. Law, S. K., and Levine, R. P., 1977, Interaction between the third complement protein and cell surface macromolecules, Proc. Natl. Acad. Sci. (USA) 74: 2701.CrossRefGoogle Scholar
  45. Law, S. K., Fearon, D. T., and Levine, R. P., 1979a, Action of the C3b-inactivator on cellbound C3b, J. Immunol. 122: 759.PubMedGoogle Scholar
  46. Law, S. K., Lichtenberg, N. A., and Levine, R. P., 1979b, Evidence for an ester linkage between the labile binding site of C3b and receptive surfaces, J. Immunol. 123:1388.PubMedGoogle Scholar
  47. Lawrence, W. D., Packman, C. H., Rowe, C. H., and Lichtman, M. A., 1981, Attachment of particle-bound IgG and complement to human neutrophils, Blood 58: 772.PubMedGoogle Scholar
  48. Lehmeyer, J. E., and Johnston, R. B., Jr., 1978, Effect of anti-inflammatory drugs and agents that elevate intracellular cyclic AMP on the release of toxic oxygen metabolites by phagocytes: Studies in a model of tissue-bound IgG, Clin. Immunol. Immunopathol. 9: 482.PubMedCrossRefGoogle Scholar
  49. Leslie, R. G. Q., and Cohen, S., 1977, Comparison of the cytophilic activities of guinea pig IgG1 and IgG2 antibodies, Eur. J. Immunol. 6: 848.CrossRefGoogle Scholar
  50. Loube, S. R., and Dorrington, K. J., 1980, Isolation of biosynthetically-labeled Fc-binding proteins from detergent lysates and spent culture fluid of a macrophage-like cell line (P388D1), J. Immunol. 125: 970.PubMedGoogle Scholar
  51. Loube, S. R., McNabb, T. C., and Dorrington, K. J., 1978, Isolation of an Fc-binding protein from the cell membrane of a macrophage-like cell line (P388D1) after detergent solubilization, J. Immunol. 120: 709.PubMedGoogle Scholar
  52. Matthews, T. J., Collins, J. J., Roloson, G. J., Thiel, H.-J., and Bolognesi, D. P., 1981, Immunologic control of the ascites form of murine adenocarcinoma 755. IV. Characterization of the protective antibody in hyperimmune serum, J. Immunol. 126: 2332.PubMedGoogle Scholar
  53. Mellman, I. S., and Unkeless, J. C., 1980, Purification of a functional mouse Fc receptor through the use of a monoclonal antibody, J. Exp. Med. 152: 580.CrossRefGoogle Scholar
  54. Mellman, I. S., Steinman, R. M., Unkeless, J. C., and Cohn, Z. A., 1980, Selective iodination and polypeptide composition of pinocytic vesicles, J. Cell. Biol. 86: 712.PubMedCrossRefGoogle Scholar
  55. Mellman, I. S., Plutner, H., Steinman, R. M., Unkeless, J. C., and Cohn, Z. A., 1983, Internalization and degradation of macrophage Fc receptors during receptor-mediated phagocytosis, J. Cell. Biol. 96: 887.PubMedCrossRefGoogle Scholar
  56. Metchnikoff, E., 1887, Sur la lutta des cellules de l’organismes centre l’invasion des microbes, Ann. Inst. Pasteur 1: 321.Google Scholar
  57. Metzger, H., 1978, The IgE-mast cell system as a paradigm for the study of antibody mechanisms, Immunol. Rev. 41:186.PubMedCrossRefGoogle Scholar
  58. 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.PubMedCrossRefGoogle Scholar
  59. Michl, J., Unkeless, J. C., Pieczonka, M. M., and Silverstein, S. C., 1983, Modulation of Fc receptors of mononuclear phagocytes by immobilized antigen-antibody complexes. Quantitative analysis of the relationship between ligand concentration and Fc receptor response, J. Exp. Med. 157: 1746.PubMedCrossRefGoogle Scholar
  60. Muschel, R. J., Rosen, N., and Bloom, B. R., 1977, Isolation of variants in phagocytosis of a macrophage-like continuous cell line, J. Exp. Med. 145: 175.PubMedCrossRefGoogle Scholar
  61. Nitta, T., and Suzuki, T., 1982, Biochemical signals transmitted by Fc receptors: Triggering mechanisms of the increased synthesis of adenosine-3’, 5’-cyclic monophosphate mediated by Fcγ2a and Fcγ2b receptors of a murine macrophage-like cell line (P388D1), J. Immunol. 129: 2708.PubMedGoogle Scholar
  62. Nuttal, G., 1888, Experimente uber die bacterienfeindlichen Einflusse des thierischen Korp ers, Z. Hyg. IngektKr. 4: 353.Google Scholar
  63. Ralph, P., Nakoinz, I., Diamond, B., and Yelton, D., 1980, All classes of murine IgG antibody mediate macrophage phagocytosis and lysis of erythrocytes, J. Immunol. 125: 1885.PubMedGoogle Scholar
  64. Reaven, E. P., and Axline, S. G., 1973, Subplasmalemmal microfilaments and microtubules in resting and phagocytizing cultivated macrophages, J. Cell Biol. 59: 12.PubMedCrossRefGoogle Scholar
  65. 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.PubMedGoogle Scholar
  66. Schneider, R. J., Atkinson, J. P., Krause, V., and Kulczycki, 1981, Characterization of ligand-binding activity of isolated murine Fc receptor, J. Immunol. 126: 735.PubMedGoogle Scholar
  67. Segal, D. M., and Titus, J. A., 1978, The subclass specificity for the binding of murine myeloma proteins to macrophage and lymphocyte cell lines and to normal spleen cells, J. Immunol. 120: 1395.PubMedGoogle Scholar
  68. Springer, T. A., Galfre, G., Secher, D. S., and Milstein, C., 1979, Mac-1: A macrophage differentiation antigen identified by monoclonal antibody, Eur. J. Immunol. 9: 301.PubMedCrossRefGoogle Scholar
  69. Springer, T. A., Davignon, D., Ho, M.-K., Kurzinger, K., Martz, E., and Sanches-Madrid, F., 1982, LFA-1 and Lyt-2,3, molecules associated with T lymphocyte-mediated killing; and Mac-1, an LFA-1 homologue associated with complement receptor functions, Immunol. Rev. 68: 171.PubMedCrossRefGoogle Scholar
  70. Suzuki, T., Tatsuo, S-T., and Nitta, T., 1982, Biochemical signal transmitted by Fc receptors: Phospholipase A2 activity of Fc 2b receptor of murine macrophage cell line P388D1, Proc. Natl. Acad. Sci. (USA) 79: 591.CrossRefGoogle Scholar
  71. Tack, B. F., Harrison, R. A., Janatova, J., Thomas, M. L., and Prahl, J. W., 1980, Evidence for presence of an internal thiolester bond in third component of human complement, Proc. Natl. Acad. Sci. (USA) 77: 5764.CrossRefGoogle Scholar
  72. Trowbridge, I. S., and Omary, M. B., 1981, Molecular complexity of leukocyte surface glycoproteins related to the macrophage differentiation antigen, Mac-1, J. Exp. Med. 154: 1517.PubMedCrossRefGoogle Scholar
  73. Unkeless, J. C., 1979, Characterization of a monoclonal antibody directed against the mouse macrophage and lymphocyte Fc receptor, J. Exp. Med. 150: 580.PubMedCrossRefGoogle Scholar
  74. Unkeless, J. C., and Eisen, H. N., 1975, Binding of monomeric immunoglobulins to Fc receptors of mouse macrophages, J. Exp. Med. 142: 1520.PubMedCrossRefGoogle Scholar
  75. Vogel, S. N., Finbloom, D. S., English, D. L., Rosenstreich, D. L., and Langreth, S. G., 1983, Interferon-induced enhancement of macrophage Fc receptor expression: B interferon treatment of C3H/HeJ macrophages results in increased numbers and density of Fc receptors, J. Immunol. 130: 1210.PubMedGoogle Scholar
  76. Walker, W. S., 1976, Separate Fc receptors for Immunoglobulins IgG2a and IgG2b on an established cell line of mouse macrophages, J. Immunol. 116: 911.PubMedGoogle Scholar
  77. Walker, W. S., 1977, Mediation of macrophage cytolytic and phagocytic activities by antibodies of different classes and class-specific Fc receptors, J. Immunol. 119: 367.PubMedGoogle Scholar
  78. Wright, A. E., and Douglas, S. R., 1903, An experimental investigation of the role of the body fluids in connection with phagocytosis, Proc. R. Soc. (Lond) 72: 357.CrossRefGoogle Scholar
  79. Wright, S. D., and Silverstein, S. C., 1982a, Phagocytosiing macrophages exclude soluble macromolecules from the zone of contact with ligand-coated targets, J. Cell Biol. 95: 433a.Google Scholar
  80. Wright, S. D., and Silverstein, S. C., 1982b, Tumor-promoting phorbol esters stimulate C3b and C3b’ receptor-mediated phagocytosis in cultured human monocytes, J. Exp. Med. 156: 1149.PubMedCrossRefGoogle Scholar
  81. Wright, S. D., and Silverstein, S. C., 1983, Receptors for C3b and C3bi promote phagocytosis but not the release of toxic oxygen from human phagocytes, J. Exp. Med. 158: 2016.PubMedCrossRefGoogle Scholar
  82. Wright, S. D., Van Voorhis, W. C., and Silverstein, S. C., 1983a, Identification of the C3b’ receptor on human leukocytes using a monoclonal antibody, Fed. Proc. 42: 1079.Google Scholar
  83. Wright, S. D., Rao, P. E., Van Voorhis, W. C., Iida, K., Craigmyle, L. S., Goldstein, G., and Silverstein, S. C., 1983b, Identification of the C3bi receptor of human monocytes and macrophages with monoclonal antibodies, Proc. Natl. Acad. Sci. (USA) 80: 5099.Google Scholar
  84. Yodoi, J., and Ishizaka, K., 1979a, Lymphocytes bearing Fc receptors for IgE. I. Presence of human and rat T lymphocytes with Fce receptors, J. Immunol. 122: 2577.PubMedGoogle Scholar
  85. Yodoi, J., and Ishizaka, K., 1979b, Lymphocytes bearing receptors for IgE. III. Transition of Fc R (+) cells to FceR (+) cells by IgE, J. Immunol. 123:2004.Google Scholar
  86. Yoshie, O., Mellman, I., Broeze, R. J., Garcia-Blanco, M., and Lengyel, P., 1982, Interferon action: Effect of of mouse a and B interferons on rosette formation, phagocytosis, and surface antigen expression of cell of the macrophage type cell line RAW 309 Cr. 1, Cell. Immunol. 73:128.PubMedCrossRefGoogle Scholar
  87. Young, J. D.-E., Unkeless, J. C., Kaback, H. R., and Cohn, Z. A., 1983a, Macrophage membrane potential changes associated with 2b/1 Fc receptor-ligand binding, Proc. Natl. Acad. Sci. (USA) 80:1357.CrossRefGoogle Scholar
  88. Young, J. D.-E., Unkeless, J. C., Kaback, H. R., and Cohn, Z. A., 1983b, Mouse macrophage Fc receptor for IgG 2b/1 in artificial and plasma membrane vesicles functions as a liganddependent ionophore, Proc. Natl. Acad. Sci. (USA) 80:1636.CrossRefGoogle Scholar
  89. Young, J. D.-E., Unkeless, J. C., Young, T. M., Mauro, A., and Cohn, Z. A., 1983c, Role for mouse macrophage IgG Fc receptor as ligand-dependent ion channel, Nature 306:186.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • Jay C. Unkeless
    • 1
  • Samuel D. Wright
    • 1
  1. 1.Department of Cellular Physiology and ImmunologyRockefeller UniversityNew YorkUSA

Personalised recommendations