Abstract
We have evaluated the capacity of the three major classes of human Fc gamma R to mediate phagocytosis by measuring the ability of adherent phagocytes to internalize erythrocytes coated with anti-Fc gamma R mAb. Five different cell types were studied, freshly purified monocytes, cultured monocytes, alveolar macrophages, freshly purified polymorphonuclear neutrophilic leukocytes, and PMNs cultured in IFN- gamma. Fc gamma RI and Fc gamma RII on whichever cells they were expressed were capable of phagocytosing anti-Fc gamma R mAb-coated erythrocytes. Furthermore, Fc gamma RIII on mononuclear phagocytes, which appears to be a conventional integral membrane protein that spans the lipid bilayer, was capable of phagocytosing anti-Fc gamma RIII- coated erythrocytes. However, Fc gamma RIII on neutrophils, a molecule linked to the membrane by a phosphatidylinositol-glycan moiety, although binding anti-Fc gamma RIII-coated erythrocytes vigorously was incapable of mounting a phagocytic response. This deficiency correlates with the limited capacity of Fc gamma RIII on neutrophils to mediate superoxide generation and antibody-dependent cell-mediated cytotoxicity and it may be related to the unique structural features of Fc gamma RIII.
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- Anderson C. L., Guyre P. M., Whitin J. C., Ryan D. H., Looney R. J., Fanger M. W. Monoclonal antibodies to Fc receptors for IgG on human mononuclear phagocytes. Antibody characterization and induction of superoxide production in a monocyte cell line. J Biol Chem. 1986 Sep 25;261(27):12856–12864. [PubMed] [Google Scholar]
- Brooks D. G., Qiu W. Q., Luster A. D., Ravetch J. V. Structure and expression of human IgG FcRII(CD32). Functional heterogeneity is encoded by the alternatively spliced products of multiple genes. J Exp Med. 1989 Oct 1;170(4):1369–1385. doi: 10.1084/jem.170.4.1369. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clark S. J., Law D. A., Paterson D. J., Puklavec M., Williams A. F. Activation of rat T lymphocytes by anti-CD2 monoclonal antibodies. J Exp Med. 1988 Jun 1;167(6):1861–1872. doi: 10.1084/jem.167.6.1861. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clarkson S. B., Ory P. A. CD16. Developmentally regulated IgG Fc receptors on cultured human monocytes. J Exp Med. 1988 Feb 1;167(2):408–420. doi: 10.1084/jem.167.2.408. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fanger M. W., Shen L., Graziano R. F., Guyre P. M. Cytotoxicity mediated by human Fc receptors for IgG. Immunol Today. 1989 Mar;10(3):92–99. doi: 10.1016/0167-5699(89)90234-X. [DOI] [PubMed] [Google Scholar]
- Fleit H. B., Wright S. D., Unkeless J. C. Human neutrophil Fc gamma receptor distribution and structure. Proc Natl Acad Sci U S A. 1982 May;79(10):3275–3279. doi: 10.1073/pnas.79.10.3275. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gendelman H. E., Orenstein J. M., Martin M. A., Ferrua C., Mitra R., Phipps T., Wahl L. A., Lane H. C., Fauci A. S., Burke D. S. Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes. J Exp Med. 1988 Apr 1;167(4):1428–1441. doi: 10.1084/jem.167.4.1428. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Graham I. L., Gresham H. D., Brown E. J. An immobile subset of plasma membrane CD11b/CD18 (Mac-1) is involved in phagocytosis of targets recognized by multiple receptors. J Immunol. 1989 Apr 1;142(7):2352–2358. [PubMed] [Google Scholar]
- Graziano R. F., Fanger M. W. Fc gamma RI and Fc gamma RII on monocytes and granulocytes are cytotoxic trigger molecules for tumor cells. J Immunol. 1987 Nov 15;139(10):3536–3541. [PubMed] [Google Scholar]
- He Q., Beyers A. D., Barclay A. N., Williams A. F. A role in transmembrane signaling for the cytoplasmic domain of the CD2 T lymphocyte surface antigen. Cell. 1988 Sep 23;54(7):979–984. doi: 10.1016/0092-8674(88)90112-2. [DOI] [PubMed] [Google Scholar]
- Huizinga T. W., van Kemenade F., Koenderman L., Dolman K. M., von dem Borne A. E., Tetteroo P. A., Roos D. The 40-kDa Fc gamma receptor (FcRII) on human neutrophils is essential for the IgG-induced respiratory burst and IgG-induced phagocytosis. J Immunol. 1989 Apr 1;142(7):2365–2369. [PubMed] [Google Scholar]
- Huizinga T. W., van der Schoot C. E., Jost C., Klaassen R., Kleijer M., von dem Borne A. E., Roos D., Tetteroo P. A. The PI-linked receptor FcRIII is released on stimulation of neutrophils. Nature. 1988 Jun 16;333(6174):667–669. doi: 10.1038/333667a0. [DOI] [PubMed] [Google Scholar]
- Hunninghake G. W., Gadek J. E., Kawanami O., Ferrans V. J., Crystal R. G. Inflammatory and immune processes in the human lung in health and disease: evaluation by bronchoalveolar lavage. Am J Pathol. 1979 Oct;97(1):149–206. [PMC free article] [PubMed] [Google Scholar]
- Jones D. H., Nusbacher J., Anderson C. L. Fc receptor-mediated binding and endocytosis by human mononuclear phagocytes: monomeric IgG is not endocytosed by U937 cells and monocytes. J Cell Biol. 1985 Feb;100(2):558–564. doi: 10.1083/jcb.100.2.558. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karpovsky B., Titus J. A., Stephany D. A., Segal D. M. Production of target-specific effector cells using hetero-cross-linked aggregates containing anti-target cell and anti-Fc gamma receptor antibodies. J Exp Med. 1984 Dec 1;160(6):1686–1701. doi: 10.1084/jem.160.6.1686. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Looney R. J., Abraham G. N., Anderson C. L. Human monocytes and U937 cells bear two distinct Fc receptors for IgG. J Immunol. 1986 Mar 1;136(5):1641–1647. [PubMed] [Google Scholar]
- Looney R. J., Ryan D. H., Takahashi K., Fleit H. B., Cohen H. J., Abraham G. N., Anderson C. L. Identification of a second class of IgG Fc receptors on human neutrophils. A 40 kilodalton molecule also found on eosinophils. J Exp Med. 1986 Apr 1;163(4):826–836. doi: 10.1084/jem.163.4.826. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mishell R. I., Dutton R. W. Immunization of dissociated spleen cell cultures from normal mice. J Exp Med. 1967 Sep 1;126(3):423–442. doi: 10.1084/jem.126.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perussia B., Dayton E. T., Lazarus R., Fanning V., Trinchieri G. Immune interferon induces the receptor for monomeric IgG1 on human monocytic and myeloid cells. J Exp Med. 1983 Oct 1;158(4):1092–1113. doi: 10.1084/jem.158.4.1092. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ravetch J. V., Perussia B. Alternative membrane forms of Fc gamma RIII(CD16) on human natural killer cells and neutrophils. Cell type-specific expression of two genes that differ in single nucleotide substitutions. J Exp Med. 1989 Aug 1;170(2):481–497. doi: 10.1084/jem.170.2.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Salmon J. E., Kapur S., Kimberly R. P. Opsonin-independent ligation of Fc gamma receptors. The 3G8-bearing receptors on neutrophils mediate the phagocytosis of concanavalin A-treated erythrocytes and nonopsonized Escherichia coli. J Exp Med. 1987 Dec 1;166(6):1798–1813. doi: 10.1084/jem.166.6.1798. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Selvaraj P., Rosse W. F., Silber R., Springer T. A. The major Fc receptor in blood has a phosphatidylinositol anchor and is deficient in paroxysmal nocturnal haemoglobinuria. Nature. 1988 Jun 9;333(6173):565–567. doi: 10.1038/333565a0. [DOI] [PubMed] [Google Scholar]
- Shen L., Guyre P. M., Anderson C. L., Fanger M. W. Heteroantibody-mediated cytotoxicity: antibody to the high affinity Fc receptor for IgG mediates cytotoxicity by human monocytes that is enhanced by interferon-gamma and is not blocked by human IgG. J Immunol. 1986 Dec 1;137(11):3378–3382. [PubMed] [Google Scholar]
- Shen L., Guyre P. M., Fanger M. W. Polymorphonuclear leukocyte function triggered through the high affinity Fc receptor for monomeric IgG. J Immunol. 1987 Jul 15;139(2):534–538. [PubMed] [Google Scholar]
- Tosi M. F., Berger M. Functional differences between the 40 kDa and 50 to 70 kDa IgG Fc receptors on human neutrophils revealed by elastase treatment and antireceptor antibodies. J Immunol. 1988 Sep 15;141(6):2097–2103. [PubMed] [Google Scholar]
- Unkeless J. C. Function and heterogeneity of human Fc receptors for immunoglobulin G. J Clin Invest. 1989 Feb;83(2):355–361. doi: 10.1172/JCI113891. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Willis H. E., Browder B., Feister A. J., Mohanakumar T., Ruddy S. Monoclonal antibody to human IgG Fc receptors. Cross-linking of receptors induces lysosomal enzyme release and superoxide generation by neutrophils. J Immunol. 1988 Jan 1;140(1):234–239. [PubMed] [Google Scholar]
- Wright S. D. Methods for the study of receptor-mediated phagocytosis. Methods Enzymol. 1986;132:204–221. doi: 10.1016/s0076-6879(86)32009-3. [DOI] [PubMed] [Google Scholar]
