Skip to main content
NCBI home page
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1992 May;51(5):594–599. doi: 10.1136/ard.51.5.594

Impairment of neutrophil Fc gamma receptor mediated transmembrane signalling in active rheumatoid arthritis.

N J Goulding 1, P M Guyre 1
PMCID: PMC1005688  PMID: 1535494

Abstract

Neutrophil Fc gamma receptor (Fc gamma R) signalling responses were compared in healthy subjects, patients with definite rheumatoid arthritis (RA), ankylosing spondylitis, and osteoarthritis. The patients with A were subdivided into those with active synovitis and those with quiescent disease. Basal intracellular calcium ion concentrations in patients with inactive RA were significantly higher than in control subjects, which in turn were greater than in patients with active RA. Transient cytosolic calcium ion fluxes were observed after binding Fc gamma RII or Fc gamma RIII with specific monoclonal antibodies and cross linking with the F(ab')2 fragment of antimouse IgG. Response times were significantly faster for Fc gamma RII than for Fc gamma RIII. Peak concentrations of intracellular calcium ions after neutrophil stimulation were comparable for Fc gamma RII and RIII in healthy subjects. Neutrophils in patients with ankylosing spondylitis and osteoarthritis responded to Fc gamma R triggering, but in the group with active RA fluxes of calcium ions were severely depressed. Neutrophils isolated from patients with RA with quiescent disease showed exaggerated responses when compared with controls. Expression of all three Fc gamma R types on neutrophils from patients with active RA, as measured by monoclonal antibody binding, was comparable with control cells. Impairment of neutrophil Fc gamma R cytosolic signalling in active RA could reflect a receptor signalling defect with potential effects on Fc mediated functions, or a fundamental defect in calcium ion homeostasis within these cells.

Full text

PDF
594

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berridge M. J., Irvine R. F. Inositol phosphates and cell signalling. Nature. 1989 Sep 21;341(6239):197–205. doi: 10.1038/341197a0. [DOI] [PubMed] [Google Scholar]
  2. Bijsterbosch M. K., Rigley K. P., Klaus G. G. Cross-linking of surface immunoglobulin on B lymphocytes induces both intracellular Ca2+ release and Ca2+ influx: analysis with indo-1. Biochem Biophys Res Commun. 1986 May 29;137(1):500–506. doi: 10.1016/0006-291x(86)91238-6. [DOI] [PubMed] [Google Scholar]
  3. Breedveld F. C., van den Barselaar M. T., Leigh P. C., Cats A., van Furth R. Phagocytosis and intracellular killing by polymorphonuclear cells from patients with rheumatoid arthritis and Felty's syndrome. Arthritis Rheum. 1985 Apr;28(4):395–404. doi: 10.1002/art.1780280407. [DOI] [PubMed] [Google Scholar]
  4. Brown K. A. The polymorphonuclear cell in rheumatoid arthritis. Br J Rheumatol. 1988 Apr;27(2):150–155. doi: 10.1093/rheumatology/27.2.150. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Ferrante A., Thong Y. H. A rapid one-step procedure for purification of mononuclear and polymorphonuclear leukocytes from human blood using a modification of the Hypaque-Ficoll technique. J Immunol Methods. 1978;24(3-4):389–393. doi: 10.1016/0022-1759(78)90143-6. [DOI] [PubMed] [Google Scholar]
  7. Fällman M., Lew D. P., Stendahl O., Andersson T. Receptor-mediated phagocytosis in human neutrophils is associated with increased formation of inositol phosphates and diacylglycerol. Elevation in cytosolic free calcium and formation of inositol phosphates can be dissociated from accumulation of diacylglycerol. J Clin Invest. 1989 Sep;84(3):886–891. doi: 10.1172/JCI114249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gill D. L., Mullaney J. M., Ghosh T. K. Intracellular calcium translocation: mechanism of activation by guanine nucleotides and inositol phosphates. J Exp Biol. 1988 Sep;139:105–133. doi: 10.1242/jeb.139.1.105. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Gresham H. D., Zheleznyak A., Mormol J. S., Brown E. J. Studies on the molecular mechanisms of human neutrophil Fc receptor-mediated phagocytosis. Evidence that a distinct pathway for activation of the respiratory burst results in reactive oxygen metabolite-dependent amplification of ingestion. J Biol Chem. 1990 May 15;265(14):7819–7826. [PubMed] [Google Scholar]
  11. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. King S. L., Parker J., Cooper R., Sturrock R., Gemmell C. G. Polymorphonuclear leucocyte function in rheumatoid arthritis. Br J Rheumatol. 1986 Feb;25(1):26–33. doi: 10.1093/rheumatology/25.1.26. [DOI] [PubMed] [Google Scholar]
  15. Le Bouteiller P. P., Mishal Z., Lemonnier F. A., Kourilsky F. M. Quantification by flow cytofluorimetry of HLA class I molecules at the surface of murine cells transformed by cloned HLA genes. J Immunol Methods. 1983 Jul 29;61(3):301–315. doi: 10.1016/0022-1759(83)90224-7. [DOI] [PubMed] [Google Scholar]
  16. Reibman J., Haines K. A., Gude D., Weissmann G. Differences in signal transduction between Fc gamma receptors (Fc gamma RII, Fc gamma RIII) and FMLP receptors in neutrophils. Effects of colchicine on pertussis toxin sensitivity and diacylglycerol formation. J Immunol. 1991 Feb 1;146(3):988–996. [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Snyder S. H., Supattapone S. Isolation and functional characterization of an inositol trisphosphate receptor from brain. Cell Calcium. 1989 Jul;10(5):337–342. doi: 10.1016/0143-4160(89)90059-6. [DOI] [PubMed] [Google Scholar]
  20. Tiku K., Tiku M. L., Liu S., Skosey J. L. Normal human neutrophils are a source of a specific interleukin 1 inhibitor. J Immunol. 1986 May 15;136(10):3686–3692. [PubMed] [Google Scholar]
  21. Tiku K., Tiku M. L., Skosey J. L. Interleukin 1 production by human polymorphonuclear neutrophils. J Immunol. 1986 May 15;136(10):3677–3685. [PubMed] [Google Scholar]
  22. Voetman A. A., Weening R. S., Hamers M. N., Meerhof L. J., Bot A. A., Roos D. Phagocytosing human neutrophils inactivate their own granular enzymes. J Clin Invest. 1981 May;67(5):1541–1549. doi: 10.1172/JCI110185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. 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]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES