Abstract
The transmembrane isoform of Fc gamma RIII, Fc gamma RIIIA, is found on NK cells, cultured monocytes, and tissue macrophages in association with a dimer of an accessory subunit, either gamma or zeta. Functions of individual Fc receptors have been difficult to analyze due to coexpression of the receptors on hematopoietic cells and permanent cell lines expressing Fc receptors. cDNAs for the alpha and gamma subunits of Fc gamma RIIIA were cotransfected into COS-1 cells, which lack endogenous Fc receptors, to evaluate receptor-mediated phagocytosis and changes in [Ca2+]i. Transfectants both bound and phagocytosed IgG-sensitized erythrocytes and, following activation of Fc gamma RIIIA, increased [Ca2+]i. The gamma subunit was essential both for the surface expression of the receptor and for transduction of the phagocytic signal. Truncation of the gamma subunit cytoplasmic domain (amino acids 65-80) eliminated phagocytic function. Phorbol ester inhibited phagocytosis in a concentration-dependent manner, but did not affect IgG-sensitized erythrocytes binding, suggesting that a protein kinase C-dependent pathway inhibits phagocytosis. The data indicate that a tyrosine containing cytoplasmic domain within the gamma subunit is required for phagocytosis by Fc gamma RIIIA.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Amigorena S., Salamero J., Davoust J., Fridman W. H., Bonnerot C. Tyrosine-containing motif that transduces cell activation signals also determines internalization and antigen presentation via type III receptors for IgG. Nature. 1992 Jul 23;358(6384):337–341. doi: 10.1038/358337a0. [DOI] [PubMed] [Google Scholar]
- Anderson P., Caligiuri M., O'Brien C., Manley T., Ritz J., Schlossman S. F. Fc gamma receptor type III (CD16) is included in the zeta NK receptor complex expressed by human natural killer cells. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2274–2278. doi: 10.1073/pnas.87.6.2274. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bauer A., McConkey D. J., Howard F. D., Clayton L. K., Novick D., Koyasu S., Reinherz E. L. Differential signal transduction via T-cell receptor CD3 zeta 2, CD3 zeta-eta, and CD3 eta 2 isoforms. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3842–3846. doi: 10.1073/pnas.88.9.3842. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cassatella M. A., Anegón I., Cuturi M. C., Griskey P., Trinchieri G., Perussia B. Fc gamma R(CD16) interaction with ligand induces Ca2+ mobilization and phosphoinositide turnover in human natural killer cells. Role of Ca2+ in Fc gamma R(CD16)-induced transcription and expression of lymphokine genes. J Exp Med. 1989 Feb 1;169(2):549–567. doi: 10.1084/jem.169.2.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collart M. A., Belin D., Briottet C., Thorens B., Vassalli J. D., Vassalli P. Receptor-mediated phagocytosis by macrophages induces a calcium-dependent transient increase in c-fos transcription. Oncogene. 1989 Feb;4(2):237–241. [PubMed] [Google Scholar]
- Darby C., Chien P., Rossman M. D., Schreiber A. D. Monocyte/macrophage Fc gamma RIII, unlike Fc gamma RIII on neutrophils, is not a phosphatidylinositol-linked protein. Blood. 1990 Jun 15;75(12):2396–2400. [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]
- Hibbs M. L., Selvaraj P., Carpén O., Springer T. A., Kuster H., Jouvin M. H., Kinet J. P. Mechanisms for regulating expression of membrane isoforms of Fc gamma RIII (CD16). Science. 1989 Dec 22;246(4937):1608–1611. doi: 10.1126/science.2531918. [DOI] [PubMed] [Google Scholar]
- Horton R. M., Cai Z. L., Ho S. N., Pease L. R. Gene splicing by overlap extension: tailor-made genes using the polymerase chain reaction. Biotechniques. 1990 May;8(5):528–535. [PubMed] [Google Scholar]
- Huang M. M., Indik Z., Brass L. F., Hoxie J. A., Schreiber A. D., Brugge J. S. Activation of Fc gamma RII induces tyrosine phosphorylation of multiple proteins including Fc gamma RII. J Biol Chem. 1992 Mar 15;267(8):5467–5473. [PubMed] [Google Scholar]
- Indik Z., Kelly C., Chien P., Levinson A. I., Schreiber A. D. Human Fc gamma RII, in the absence of other Fc gamma receptors, mediates a phagocytic signal. J Clin Invest. 1991 Nov;88(5):1766–1771. doi: 10.1172/JCI115496. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Irving B. A., Weiss A. The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal transduction pathways. Cell. 1991 Mar 8;64(5):891–901. doi: 10.1016/0092-8674(91)90314-o. [DOI] [PubMed] [Google Scholar]
- Kruskal B. A., Sastry K., Warner A. B., Mathieu C. E., Ezekowitz R. A. Phagocytic chimeric receptors require both transmembrane and cytoplasmic domains from the mannose receptor. J Exp Med. 1992 Dec 1;176(6):1673–1680. doi: 10.1084/jem.176.6.1673. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kurosaki T., Gander I., Ravetch J. V. A subunit common to an IgG Fc receptor and the T-cell receptor mediates assembly through different interactions. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3837–3841. doi: 10.1073/pnas.88.9.3837. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kurosaki T., Ravetch J. V. A single amino acid in the glycosyl phosphatidylinositol attachment domain determines the membrane topology of Fc gamma RIII. Nature. 1989 Dec 14;342(6251):805–807. doi: 10.1038/342805a0. [DOI] [PubMed] [Google Scholar]
- Küster H., Thompson H., Kinet J. P. Characterization and expression of the gene for the human Fc receptor gamma subunit. Definition of a new gene family. J Biol Chem. 1990 Apr 15;265(11):6448–6452. [PubMed] [Google Scholar]
- Lanier L. L., Yu G., Phillips J. H. Co-association of CD3 zeta with a receptor (CD16) for IgG Fc on human natural killer cells. Nature. 1989 Dec 14;342(6251):803–805. doi: 10.1038/342803a0. [DOI] [PubMed] [Google Scholar]
- Laskin D. L., Beavis A. J., Sirak A. A., O'Connell S. M., Laskin J. D. Differentiation of U-937 histiocytic lymphoma cells towards mature neutrophilic granulocytes by dibutyryl cyclic adenosine-3',5'-monophosphate. Cancer Res. 1990 Jan 1;50(1):20–25. [PubMed] [Google Scholar]
- McGillis J. P., Sudduth-Klinger J., Harrowe G., Mitsuhashi M., Payan D. G. Transient expression of the angiotensin II receptor: a rapid and functional analysis of a calcium-mobilizing seven-transmembrane domain receptor in COS-7 cells. Biochem Biophys Res Commun. 1989 Dec 29;165(3):935–941. doi: 10.1016/0006-291x(89)92693-4. [DOI] [PubMed] [Google Scholar]
- Odin J. A., Edberg J. C., Painter C. J., Kimberly R. P., Unkeless J. C. Regulation of phagocytosis and [Ca2+]i flux by distinct regions of an Fc receptor. Science. 1991 Dec 20;254(5039):1785–1788. doi: 10.1126/science.1837175. [DOI] [PubMed] [Google Scholar]
- Park J. G., Murray R. K., Chien P., Darby C., Schreiber A. D. Conserved cytoplasmic tyrosine residues of the gamma subunit are required for a phagocytic signal mediated by Fc gamma RIIIA. J Clin Invest. 1993 Oct;92(4):2073–2079. doi: 10.1172/JCI116804. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perussia B., Ravetch J. V. Fc gamma RIII (CD16) on human macrophages is a functional product of the Fc gamma RIII-2 gene. Eur J Immunol. 1991 Feb;21(2):425–429. doi: 10.1002/eji.1830210226. [DOI] [PubMed] [Google Scholar]
- Qiu W. Q., de Bruin D., Brownstein B. H., Pearse R., Ravetch J. V. Organization of the human and mouse low-affinity Fc gamma R genes: duplication and recombination. Science. 1990 May 11;248(4956):732–735. doi: 10.1126/science.2139735. [DOI] [PubMed] [Google Scholar]
- Ra C., Jouvin M. H., Blank U., Kinet J. P. A macrophage Fc gamma receptor and the mast cell receptor for IgE share an identical subunit. Nature. 1989 Oct 26;341(6244):752–754. doi: 10.1038/341752a0. [DOI] [PubMed] [Google Scholar]
- Ra C., Jouvin M. H., Kinet J. P. Complete structure of the mouse mast cell receptor for IgE (Fc epsilon RI) and surface expression of chimeric receptors (rat-mouse-human) on transfected cells. J Biol Chem. 1989 Sep 15;264(26):15323–15327. [PubMed] [Google Scholar]
- Ravetch J. V., Kinet J. P. Fc receptors. Annu Rev Immunol. 1991;9:457–492. doi: 10.1146/annurev.iy.09.040191.002325. [DOI] [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]
- Reth M. Antigen receptor tail clue. Nature. 1989 Mar 30;338(6214):383–384. doi: 10.1038/338383b0. [DOI] [PubMed] [Google Scholar]
- Rosales C., Brown E. J. Two mechanisms for IgG Fc-receptor-mediated phagocytosis by human neutrophils. J Immunol. 1991 Jun 1;146(11):3937–3944. [PubMed] [Google Scholar]
- Schreiber A. D., Parsons J., McDermott P., Cooper R. A. Effect of corticosteroids on the human monocyte IgG and complement receptors. J Clin Invest. 1975 Nov;56(5):1189–1197. doi: 10.1172/JCI108196. [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]
- Tuijnman W. B., Capel P. J., van de Winkel J. G. Human low-affinity IgG receptor Fc gamma RIIa (CD32) introduced into mouse fibroblasts mediates phagocytosis of sensitized erythrocytes. Blood. 1992 Apr 1;79(7):1651–1656. [PubMed] [Google Scholar]
- Weiss A. Structure and function of the T cell antigen receptor. J Clin Invest. 1990 Oct;86(4):1015–1022. doi: 10.1172/JCI114803. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wirthmueller U., Kurosaki T., Murakami M. S., Ravetch J. V. Signal transduction by Fc gamma RIII (CD16) is mediated through the gamma chain. J Exp Med. 1992 May 1;175(5):1381–1390. doi: 10.1084/jem.175.5.1381. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- van de Winkel J. G., Anderson C. L. Biology of human immunoglobulin G Fc receptors. J Leukoc Biol. 1991 May;49(5):511–524. doi: 10.1002/jlb.49.5.511. [DOI] [PubMed] [Google Scholar]