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. 1997 Dec;92(4):544–552. doi: 10.1046/j.1365-2567.1997.00381.x

The high-affinity Fc gamma RI on PMN: regulation of expression and signal transduction.

F Hoffmeyer 1, K Witte 1, R E Schmidt 1
PMCID: PMC1364161  PMID: 9497497

Abstract

In this paper we report that interferon-gamma (IFN-gamma) maintains and enhances functional properties of terminally differentiated polymorphonuclear cells (PMN). Such effects are obvious when compared with untreated PMN declining in their functional response. Culture for 18 hr with 100 IU/ml of recombinant IFN-gamma resulted in the expression of about 15,000 Fc gamma RI per PMN. IFN-gamma maintained viability of PMN and prevented reduction of Fc gamma RIIIb caused by apoptosis. No alterations were found in the level of Fc gamma RIIa. Next, functional properties of Fc gamma RI were evaluated. Calcium mobilization was detected in fura-2/acetoxymethylester (AM)-loaded PMN using a spectrophotometer and the respiratory burst was measured as luminol-dependent chemiluminescence. Cross-linking of an F(ab')2 fragment of monoclonal antibody (mAb) 22.2 to Fc gamma RI gave similar results to those obtained with intact monomeric human immunoglobulin G (mhIgG) when subsequently cross-linked. Moreover, after blocking Fc gamma RIIa and Fc gamma RIIIb with respective mAb fragments, mhIgG was still effective in triggering a calcium flux demonstrating that second messenger generation was caused by Fc gamma RI engagement. Even though Fc gamma RI expression was lower than that of Fc gamma RIIa, Fc gamma RI induced a higher increase of the respiratory burst. In addition, the protein tyrosine phosphatase CD45 was able to inhibit both responses when it was co-cross-linked with CD64, suggesting involvement of tyrosine phosphorylation in early signalling steps.

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Selected References

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  1. Akerley W. L., 3rd, Guyre P. M., Davis B. H. Neutrophil activation through high-affinity Fc gamma receptor using a monomeric antibody with unique properties. Blood. 1991 Feb 1;77(3):607–615. [PubMed] [Google Scholar]
  2. Buckle A. M., Hogg N. The effect of IFN-gamma and colony-stimulating factors on the expression of neutrophil cell membrane receptors. J Immunol. 1989 Oct 1;143(7):2295–2301. [PubMed] [Google Scholar]
  3. Cambier J. C. Antigen and Fc receptor signaling. The awesome power of the immunoreceptor tyrosine-based activation motif (ITAM). J Immunol. 1995 Oct 1;155(7):3281–3285. [PubMed] [Google Scholar]
  4. Cohen J. J. Apoptosis. Immunol Today. 1993 Mar;14(3):126–130. doi: 10.1016/0167-5699(93)90214-6. [DOI] [PubMed] [Google Scholar]
  5. Colotta F., Re F., Polentarutti N., Sozzani S., Mantovani A. Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products. Blood. 1992 Oct 15;80(8):2012–2020. [PubMed] [Google Scholar]
  6. Corvaïa N., Reischl I. G., Kroemer E., Mudde G. C. Modulation of Fc gamma receptor-mediated early events by the tyrosine phosphatase CD45 in primary human monocytes. Consequences for interleukin-6 production. Eur J Immunol. 1995 Mar;25(3):738–744. doi: 10.1002/eji.1830250317. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Ding J., Badwey J. A. Effects of antagonists of protein phosphatases on superoxide release by neutrophils. J Biol Chem. 1992 Mar 25;267(9):6442–6448. [PubMed] [Google Scholar]
  9. Durden D. L., Rosen H., Michel B. R., Cooper J. A. Protein tyrosine phosphatase inhibitors block myeloid signal transduction through the Fc gamma RI receptor. Exp Cell Res. 1994 Mar;211(1):150–162. doi: 10.1006/excr.1994.1071. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Guyre P. M., Campbell A. S., Kniffin W. D., Fanger M. W. Monocytes and polymorphonuclear neutrophils of patients with streptococcal pharyngitis express increased numbers of type I IgG Fc receptors. J Clin Invest. 1990 Dec;86(6):1892–1896. doi: 10.1172/JCI114921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Harvath L., Balke J. A., Christiansen N. P., Russell A. A., Skubitz K. M. Selected antibodies to leukocyte common antigen (CD45) inhibit human neutrophil chemotaxis. J Immunol. 1991 Feb 1;146(3):949–957. [PubMed] [Google Scholar]
  13. Hazenbos W. L., Gessner J. E., Hofhuis F. M., Kuipers H., Meyer D., Heijnen I. A., Schmidt R. E., Sandor M., Capel P. J., Daëron M. Impaired IgG-dependent anaphylaxis and Arthus reaction in Fc gamma RIII (CD16) deficient mice. Immunity. 1996 Aug;5(2):181–188. doi: 10.1016/s1074-7613(00)80494-x. [DOI] [PubMed] [Google Scholar]
  14. Hoffmeyer F., Witte K., Gebhardt U., Schmidt R. E. The low affinity Fc gamma RIIa and Fc gamma RIIIb on polymorphonuclear neutrophils are differentially regulated by CD45 phosphatase. J Immunol. 1995 Oct 15;155(8):4016–4023. [PubMed] [Google Scholar]
  15. Homburg C. H., de Haas M., von dem Borne A. E., Verhoeven A. J., Reutelingsperger C. P., Roos D. Human neutrophils lose their surface Fc gamma RIII and acquire Annexin V binding sites during apoptosis in vitro. Blood. 1995 Jan 15;85(2):532–540. [PubMed] [Google Scholar]
  16. 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]
  17. Huizinga T. W., Roos D., von dem Borne A. E. Neutrophil Fc-gamma receptors: a two-way bridge in the immune system. Blood. 1990 Mar 15;75(6):1211–1214. [PubMed] [Google Scholar]
  18. Huizinga T. W., de Haas M., Kleijer M., Nuijens J. H., Roos D., von dem Borne A. E. Soluble Fc gamma receptor III in human plasma originates from release by neutrophils. J Clin Invest. 1990 Aug;86(2):416–423. doi: 10.1172/JCI114727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Hundt M., Schmidt R. E. The glycosylphosphatidylinositol-linked Fc gamma receptor III represents the dominant receptor structure for immune complex activation of neutrophils. Eur J Immunol. 1992 Mar;22(3):811–816. doi: 10.1002/eji.1830220327. [DOI] [PubMed] [Google Scholar]
  21. Hundt M., Zielinska-Skowronek M., Schmidt R. E. Fc gamma receptor activation of neutrophils in cryoglobulin-induced leukocytoclastic vasculitis. Arthritis Rheum. 1993 Jul;36(7):974–982. doi: 10.1002/art.1780360715. [DOI] [PubMed] [Google Scholar]
  22. Kumaratilake L. M., Ferrante A., Rzepczyk C. The role of T lymphocytes in immunity to Plasmodium falciparum. Enhancement of neutrophil-mediated parasite killing by lymphotoxin and IFN-gamma: comparisons with tumor necrosis factor effects. J Immunol. 1991 Jan 15;146(2):762–767. [PubMed] [Google Scholar]
  23. Lee A., Whyte M. K., Haslett C. Inhibition of apoptosis and prolongation of neutrophil functional longevity by inflammatory mediators. J Leukoc Biol. 1993 Oct;54(4):283–288. [PubMed] [Google Scholar]
  24. Liao F., Shin H. S., Rhee S. G. Tyrosine phosphorylation of phospholipase C-gamma 1 induced by cross-linking of the high-affinity or low-affinity Fc receptor for IgG in U937 cells. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3659–3663. doi: 10.1073/pnas.89.8.3659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Majima T., Minegishi N., Nagatomi R., Ohashi Y., Tsuchiya S., Kobayashi K., Konno T. Unusual expression of IgG Fc receptors on peripheral granulocytes from patients with leukocyte adhesion deficiency (CD11/CD18 deficiency). J Immunol. 1990 Sep 15;145(6):1694–1699. [PubMed] [Google Scholar]
  27. Moxey-Mims M. M., Frank M. M., Lin E. Y., Francis C., Gaither T. A. Increased expression of Fc gamma RI on isolated PMN from individuals of African descent. Clin Immunol Immunopathol. 1993 Oct;69(1):117–121. doi: 10.1006/clin.1993.1158. [DOI] [PubMed] [Google Scholar]
  28. Pericle F., Liu J. H., Diaz J. I., Blanchard D. K., Wei S., Forni G., Djeu J. Y. Interleukin-2 prevention of apoptosis in human neutrophils. Eur J Immunol. 1994 Feb;24(2):440–444. doi: 10.1002/eji.1830240226. [DOI] [PubMed] [Google Scholar]
  29. Perussia B., Kobayashi M., Rossi M. E., Anegon I., Trinchieri G. Immune interferon enhances functional properties of human granulocytes: role of Fc receptors and effect of lymphotoxin, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor. J Immunol. 1987 Feb 1;138(3):765–774. [PubMed] [Google Scholar]
  30. Petroni K. C., Shen L., Guyre P. M. Modulation of human polymorphonuclear leukocyte IgG Fc receptors and Fc receptor-mediated functions by IFN-gamma and glucocorticoids. J Immunol. 1988 May 15;140(10):3467–3472. [PubMed] [Google Scholar]
  31. Pfefferkorn L. C., Fanger M. W. Transient activation of the NADPH oxidase through Fc gamma RI. Oxidase deactivation precedes internalization of cross-linked receptors. J Immunol. 1989 Oct 15;143(8):2640–2649. [PubMed] [Google Scholar]
  32. Radeke H. H., Gessner J. E., Uciechowski P., Mägert H. J., Schmidt R. E., Resch K. Intrinsic human glomerular mesangial cells can express receptors for IgG complexes (hFc gamma RIII-A) and the associated Fc epsilon RI gamma-chain. J Immunol. 1994 Aug 1;153(3):1281–1292. [PubMed] [Google Scholar]
  33. Rankin B. M., Yocum S. A., Mittler R. S., Kiener P. A. Stimulation of tyrosine phosphorylation and calcium mobilization by Fc gamma receptor cross-linking. Regulation by the phosphotyrosine phosphatase CD45. J Immunol. 1993 Jan 15;150(2):605–616. [PubMed] [Google Scholar]
  34. Ravetch J. V. Fc receptors: rubor redux. Cell. 1994 Aug 26;78(4):553–560. doi: 10.1016/0092-8674(94)90521-5. [DOI] [PubMed] [Google Scholar]
  35. Scholl P. R., Ahern D., Geha R. S. Protein tyrosine phosphorylation induced via the IgG receptors Fc gamma Ri and Fc gamma RII in the human monocytic cell line THP-1. J Immunol. 1992 Sep 1;149(5):1751–1757. [PubMed] [Google Scholar]
  36. 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]
  37. 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]
  38. Squier M. K., Sehnert A. J., Cohen J. J. Apoptosis in leukocytes. J Leukoc Biol. 1995 Jan;57(1):2–10. doi: 10.1002/jlb.57.1.2. [DOI] [PubMed] [Google Scholar]
  39. Tamm A., Kister A., Nolte K. U., Gessner J. E., Schmidt R. E. The IgG binding site of human FcgammaRIIIB receptor involves CC' and FG loops of the membrane-proximal domain. J Biol Chem. 1996 Feb 16;271(7):3659–3666. doi: 10.1074/jbc.271.7.3659. [DOI] [PubMed] [Google Scholar]
  40. Tamm A., Schmidt R. E. The binding epitopes of human CD16 (Fc gamma RIII) monoclonal antibodies. Implications for ligand binding. J Immunol. 1996 Aug 15;157(4):1576–1581. [PubMed] [Google Scholar]
  41. Whyte M. K., Meagher L. C., MacDermot J., Haslett C. Impairment of function in aging neutrophils is associated with apoptosis. J Immunol. 1993 Jun 1;150(11):5124–5134. [PubMed] [Google Scholar]
  42. 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]
  43. van de Winkel J. G., Tax W. J., Jacobs C. W., Huizinga T. W., Willems P. H. Cross-linking of both types of IgG Fc receptors, Fc gamma RI and Fc gamma RII, enhances intracellular free Ca2+ in the monocytic cell line U937. Scand J Immunol. 1990 Mar;31(3):315–325. doi: 10.1111/j.1365-3083.1990.tb02774.x. [DOI] [PubMed] [Google Scholar]

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