Subscribe to RSS
DOI: 10.1055/s-0038-1650339
Characterization of Fcγ Receptors on Human Megakaryocytes
Publication History
Received 21 June 1995
Accepted after resubmission 18 December 1995
Publication Date:
10 July 2018 (online)
Summary
Megakaryocyte and platelet Fcγ receptors (FcR) are of importance in the pathophysiology of immune complex-mediated thrombocytopenias such as heparin-induced thrombocytopenia. In this study, FcγR proteins and mRNAs in normal human megakaryocytes were examined. FcγR proteins were studied with immunocytochemical staining, dual colour flow cytometry and immunoprecipitation using monoclonal antibodies against FcγR I, FcγR II and FcγR III. FcγR mRNAs were measured with biotinylated cDNA or oligonucleotide probes using a novel quantitative in situ hybridization technique. Using these techniques, FcγR II protein and mRNA, but not FcγR I and FcγR III proteins and transcripts were detected in megakaryocytes. Further, transcript analysis showed that megakaryocytes contain only the transcript of FcγR IIA gene but no transcripts of FcγR IIB nor FcγR IIC genes; FcγR IIA transcripts with and without the transmembrane (TM) exon are present in approximately equal proportions. In contrast, neutrophils and macrophages also contain FcγR IIA transcript but FcγR IIA transcript with the TM exon predominates suggesting cell lineage-specific FcγR IIA expression. FcγR IIA transcript lacking the TM exon predicts the presence of a potential soluble form of FcγR in platelets and megakaryocytes which may have a physiological role as it can compete with the membrane-bound FcγR IIA for binding of IgG-containing immune complexes and thus protect these cells from excessive binding and injurious effects of immune complexes.
-
References
- 1 Anderson CL, Looney RJ. Human leucocyte IgG Fc receptors. Immunol Today 1986; 7: 264-266
- 2 Cohen L, Sharp S, Kulczycki A. Human monocytes, B lymphocytes and non-B lymphocytes, each structurally unique Fey receptors. Immunol 1983; 131: 378-383
- 3 Rosenfeld SI, Looney RJ, Leddy JP, Philip DC, Abraham GN, Anderson CL. Human platelet Fc receptor for immunoglobulin G: identification as a 40,000 molecular weight membrane protein shared by monocytes. Clin Invest 1985; 76: 2317-2322
- 4 Qui WQ, de Bruin D, Brownsterin BH, Pearse R, Ravetch JV. Organisation of the human and mouse low-affinity FcγR genes, duplication and recombination. Science 1990; 248: 732-735
- 5 Stuart SG, Trounstine ML, Vaux DJT, Koch T, Martens CL, Mellman I, Moore KW. Isolation and expression of cDNA clones encoding a human receptor for IgG (Fc gamma RII). J Exp Med 1987; 166: 1668-1684
- 6 Cassel DL, Keller MA, Surrey S, Scwartz E, Schriber AD, Rapaport EF, McKenzie SE. Differential expression of FcγR IIA, FcγR IIB and FcγR IIC in hematopoietic cells: analysis of transcripts. Mol Immunol 1993; 30: 451-460
- 7 Chong BH, Ismail F, Chesterman CN, Bemdt MC. Heparin-induced thrombocytopenia: Mechanism of interaction of the heparin-dependent antibody with patients. Br J Haematol 1989; 73: 235-240
- 8 Kelton JG, Sherrden D, Santos A, Smith J, Steeves K, Smith C, Brown C, Murphy WG. Heparin-induced thrombocytopenia: laboratory studies. Blood 1988; 72: 925-930
- 9 Chong BH, Pilgrim RL, Cooley MA, Chesterman CN. Increased expression of platelet IgG Fc receptors in immune heparin-induced thrombocytopenia. Blood 1993; 81: 988-993
- 10 Takeda A, Tuazon CV, Ennis FA. Antibody-enhanced infection by HIV-1 via Fc receptor mediated entry. Science 1989; 242: 580-583
- 11 Gewirtz AM, Boghosian-Sell L, Catani L, Ratajzak MZ, Shen YM. Expression of FcγR II and CD4 receptors by normal human megakaryocytes. Exp Haematol 1992; 20: 512-516
- 12 Micklen KJ, Stross WP, Willis AC, Cordell JL, Jones M, Maron DR. Different isoforms of human FcR II distinguished by CDW32 antibodies. J Immunol 1990; 144: 2295-2303
- 13 Wu ZH, Chesterman CN, Chong BH. Identification of IgG Fc receptor type II on human megakaryoblastic cell lines (Meg-01 and UT-7). Br J Haematol 1993; 84: 204-224
- 14 Mazur EM, Basilico D, Newton JL, Cohen JL, Charland C, Sohi PA. Isolation of large numbers of enriched human megakaryocytes from liquid cultures of normal peripheral blood progenitor cell. Blood 1990; 76: 1771-1782
- 15 Cline MJ, Golde DW. Production of colony-stimulating activity by human lymphocytes. Nature 1974; 248: 703-704
- 16 Tomer A, Harker LA, Burstein SA. Purification of human megakarycoytes by fluorescence-activated cell sorting. Blood 1987; 1735-1742
- 17 Abts H, Emmerich M, Miltenyi S, Radbruch A, Tesch H. CD20 positive human B lymphocytes separated with the magnetic cell sorter (MACS) can be induced to proliferation and antibody secretion in vitro. J Immunol Methods 1989; 125: 19-28
- 18 Tanaka H, Isohida Y, Kaneko T, Matsumoto N. Isolation of human megakaryocytes by immunomagnetic beads. Br J Haematol 1989; 73: 18-22
- 19 Phillips DR, Agin P. Platelet plasma membrane glycoproteins. Evidence for the presence of nonequivalent disulfide bonds using nonreduced two-dimenstional electrophoresis. J Biol Chem 1977; 252: 2121-2126
- 20 Markovic B, Wu ZH, Chesterman CN, Chong BH. Quantitation of FcyR II mRNA in platelets and megakaryoblastic cell lines by a new method of in situ hybridization. J Immunol Methods 1994; 172: 105-114
- 21 Peltz G, Frederick K, Anderson CL, Peterlin BM. Characterisation of the human monocyte high affinity Fc receptor (hu FcRI). Mol Immunol 1988; 25: 243-250
- 22 Hibbs ML, Bonadenna L, Scott BM, McKenzie IFC, Hogarth PM. Molecular cloning of a human immunoglobulin G Fc receptor. Proc Natl Acad Sci USA 1988; 85: 2240-2244
- 23 Ory PA, Clark OM, Kwoh EE, Clarkson SB, Goldsterin IM. Sequence of complementary RNAs that encode the NA1 and NA2 forms of Fc receptor III on human neutrophils. J Clin Invest 1989; 84: 1688-1691
- 24 Rapaport EF, Cassel DL, Walterhouse D, McKenzie SE, Surrey S, Keller MA, Schreiber AD, Schwartz E. A soluble form of the human Fc receptor FcyR IIA. Cloning, transcript analysis and detection. Exp Hematol 1993; 21: 689-696
- 25 Vaughn M, Taylor M, Mohanakumar T. Characterisation of human Fc receptors. J Immunol 1985; 135: 4059-4065
- 26 Markovic B, Wu Z, Chesterman CN, Chong BH. Quantitation of soluble and membrane bound FcyR II (CD32A) mRNA in platelets and megakaryoblastic cell line (Meg-01). Brit J Haematol (in press)
- 27 Gachet C, Astier A, de la Salle H, de la Salle C, Fridman WH, Cazanave J-P, Hanau D, Teillaud J-L. Release of FcγR IIa2 by activated platelets and inhibition of anti-CD9-mediated platelet aggregation by recombinant FcyR IIa2. Blood 1995; 85: 698-704
- 28 Chong BH, Murray B, Bemdt MC, Dunlop LC, Brighton T, Chesterman CN. Plasma P-selection is increased in thrombotic consumptive platelet disorders. Blood 1994; 83: 1535-1541