Abstract
The role of IgG receptor, Fc gamma RIII, in the triggering of neutrophil functions has been controversial. Here we show that IgM monoclonal antibodies, Leu 11b and 1D3, recognizing Fc gamma RIII, bind to human neutrophils triggering an increase in intracellular calcium concentration and release of myeloperoxidase upon degranulation but do not trigger a respiratory burst detectable as lucigenin-enhanced chemiluminescence. Although many fewer molecules of IgM monoclonal antibody, MY43, recognizing Fc alpha R, bind to the same cells they trigger a much greater increase in intracellular calcium concentration, release of myeloperoxidase and a strong respiratory burst. Since the respiratory bursts triggered by IgG and IgA are equivalent, this demonstrates that Fc gamma RII is responsible for the IgG-mediated response. IgM monoclonal antibody MC2, recognizing the abundant neutrophil cell-surface carbohydrate CD15, also triggers a small rise in intracellular calcium but no respiratory burst.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anderson C. L., Shen L., Eicher D. M., Wewers M. D., Gill J. K. Phagocytosis mediated by three distinct Fc gamma receptor classes on human leukocytes. J Exp Med. 1990 Apr 1;171(4):1333–1345. doi: 10.1084/jem.171.4.1333. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crockett-Torabi E., Fantone J. C. Soluble and insoluble immune complexes activate human neutrophil NADPH oxidase by distinct Fc gamma receptor-specific mechanisms. J Immunol. 1990 Nov 1;145(9):3026–3032. [PubMed] [Google Scholar]
- Davies E. V., Hallett M. B., Campbell A. K. Localized superoxide release by neutrophils can be provoked by a cytosolic calcium 'cloud'. Immunology. 1991 Jun;73(2):228–234. [PMC free article] [PubMed] [Google Scholar]
- Gyllenhammar H. Correlation between neutrophil superoxide formation, luminol-augmented chemiluminescence and intracellular Ca2+ levels upon stimulation with leukotriene B4, formylpeptide and phorbolester. Scand J Clin Lab Invest. 1989 Jun;49(4):317–322. doi: 10.3109/00365518909089103. [DOI] [PubMed] [Google Scholar]
- Hamada F., Aoki M., Akiyama T., Toyoshima K. Association of immunoglobulin G Fc receptor II with Src-like protein-tyrosine kinase Fgr in neutrophils. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6305–6309. doi: 10.1073/pnas.90.13.6305. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henson P. M., Johnson H. B., Spiegelberg H. L. The release of granule enzymes from human neutrophils stimulated by aggregated immunoglobulins of different classes and subclasses. J Immunol. 1972 Dec;109(6):1182–1192. [PubMed] [Google Scholar]
- Huizinga T. W., Dolman K. M., van der Linden N. J., Kleijer M., Nuijens J. H., von dem Borne A. E., Roos D. Phosphatidylinositol-linked FcRIII mediates exocytosis of neutrophil granule proteins, but does not mediate initiation of the respiratory burst. J Immunol. 1990 Feb 15;144(4):1432–1437. [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]
- Kimberly R. P., Ahlstrom J. W., Click M. E., Edberg J. C. The glycosyl phosphatidylinositol-linked Fc gamma RIIIPMN mediates transmembrane signaling events distinct from Fc gamma RII. J Exp Med. 1990 Apr 1;171(4):1239–1255. doi: 10.1084/jem.171.4.1239. [DOI] [PMC free article] [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]
- Lopez M., Olive D., Mannoni P. Analysis of cytosolic ionized calcium variation in polymorphonuclear leukocytes using flow cytometry and Indo-1 AM. Cytometry. 1989 Mar;10(2):165–173. doi: 10.1002/cyto.990100207. [DOI] [PubMed] [Google Scholar]
- Lund-Johansen F., Olweus J., Aarli A., Bjerknes R. The IgG FcRII and the PI-linked IgG FcRIII trigger cytoplasmic calcium fluxes independently in human granulocytes. Scand J Immunol. 1991 Mar;33(3):261–266. doi: 10.1111/j.1365-3083.1991.tb01771.x. [DOI] [PubMed] [Google Scholar]
- Mazengera R. L., Kerr M. A. The specificity of the IgA receptor purified from human neutrophils. Biochem J. 1990 Nov 15;272(1):159–165. doi: 10.1042/bj2720159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCarthy N. C., Albrechtsen M. T., Kerr M. A. Characterization of a human granulocyte differentiation antigen (CDw15) commonly recognized by monoclonal antibodies. Biosci Rep. 1985 Oct-Nov;5(10-11):933–941. doi: 10.1007/BF01119906. [DOI] [PubMed] [Google Scholar]
- Naziruddin B., Duffy B. F., Tucker J., Mohanakumar T. Evidence for cross-regulation of Fc gamma RIIIB (CD16) receptor-mediated signaling by Fc gamma RII (CD32) expressed on polymorphonuclear neutrophils. J Immunol. 1992 Dec 1;149(11):3702–3709. [PubMed] [Google Scholar]
- O'Flaherty J. T., Rossi A. G., Jacobson D. P., Redman J. F. Roles of Ca2+ in human neutrophil responses to receptor agonists. Biochem J. 1991 Aug 1;277(Pt 3):705–711. doi: 10.1042/bj2770705. [DOI] [PMC free article] [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]
- Salmon J. E., Brogle N. L., Edberg J. C., Kimberly R. P. Fc gamma receptor III induces actin polymerization in human neutrophils and primes phagocytosis mediated by Fc gamma receptor II. J Immunol. 1991 Feb 1;146(3):997–1004. [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. A monoclonal antibody specific for immunoglobulin A receptor triggers polymorphonuclear neutrophil superoxide release. J Leukoc Biol. 1992 Apr;51(4):373–378. doi: 10.1002/jlb.51.4.373. [DOI] [PubMed] [Google Scholar]
- Shen L., Graziano R. F., Fanger M. W. The functional properties of Fc gamma RI, II and III on myeloid cells: a comparative study of killing of erythrocytes and tumor cells mediated through the different Fc receptors. Mol Immunol. 1989 Oct;26(10):959–969. doi: 10.1016/0161-5890(89)90114-4. [DOI] [PubMed] [Google Scholar]
- Stewart W. W., Kerr M. A. The specificity of the human neutrophil IgA receptor (Fc alpha R) determined by measurement of chemiluminescence induced by serum or secretory IgA1 or IgA2. Immunology. 1990 Nov;71(3):328–334. [PMC free article] [PubMed] [Google Scholar]
- Stewart W. W., Mazengera R. L., Shen L., Kerr M. A. Unaggregated serum IgA binds to neutrophil Fc alpha R at physiological concentrations and is endocytosed but cross-linking is necessary to elicit a respiratory burst. J Leukoc Biol. 1994 Oct;56(4):481–487. doi: 10.1002/jlb.56.4.481. [DOI] [PubMed] [Google Scholar]
- Stuart S. G., Trounstine M. L., Vaux D. J., Koch T., Martens C. L., Mellman I., Moore K. W. Isolation and expression of cDNA clones encoding a human receptor for IgG (Fc gamma RII). J Exp Med. 1987 Dec 1;166(6):1668–1684. doi: 10.1084/jem.166.6.1668. [DOI] [PMC free article] [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]
- Vandenberghe P. A., Ceuppens J. L. Flow cytometric measurement of cytoplasmic free calcium in human peripheral blood T lymphocytes with fluo-3, a new fluorescent calcium indicator. J Immunol Methods. 1990 Mar 9;127(2):197–205. doi: 10.1016/0022-1759(90)90069-8. [DOI] [PubMed] [Google Scholar]
- Walker B. A., Hagenlocker B. E., Stubbs E. B., Jr, Sandborg R. R., Agranoff B. W., Ward P. A. Signal transduction events and Fc gamma R engagement in human neutrophils stimulated with immune complexes. J Immunol. 1991 Jan 15;146(2):735–741. [PubMed] [Google Scholar]
- Zeller J. M., Sullivan B. L. Monoclonal antibody to the type II Fc receptor for human IgG blocks potentiation of monocyte and neutrophil IgG-induced respiratory burst activation by aggregated C-reactive protein. Cell Immunol. 1993 Jun;149(1):144–154. doi: 10.1006/cimm.1993.1143. [DOI] [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]