Abstract
OBJECTIVE: To compare neutrophil Fc receptor (Fc gamma R) and CD59 signalling responses in normal healthy subjects and patients with active rheumatoid arthritis (RA). METHODS: Intracellular free calcium concentrations were measured in neutrophils loaded with the fluorescent calcium indicator fura-2, using a spectrofluorimeter. RESULTS: Basal intracellular calcium ion concentrations were similar in both groups when no primary antibody, CD59, or CD32 (Fc gamma RIII) antibody was added. When CD16 (Fc gamma RIII) antibody was added, there was a significantly greater basal calcium concentration in the patient group compared with the control group. Transient cytosolic calcium ion fluxes were observed after binding Fc gamma RII, Fc gamma RIII, or CD59 with specific monoclonal antibodies and cross linking with the F(ab)2 fragment of sheep antimouse IgG. Peak concentrations of intracellular free calcium, [Ca2+]i, after cross linking each of the three receptors, were comparable between normal healthy donors and patients with RA. The lag period between addition of cross linking antibodies and the increase in calcium was also similar between normal individuals and patients. CONCLUSION: Contrary to previous reports, these results demonstrate that Ca2+ signalling responses of cross linked Fc receptors in blood neutrophils from patients with RA are identical to those in neutrophils of normal subjects. Signalling responses of cross linked CD59 are also unaltered.
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Selected References
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- Al-Mohanna F. A., Hallett M. B. The use of fura-2 to determine the relationship between cytoplasmic free Ca2+ and oxidase activation in rat neutrophils. Cell Calcium. 1988 Feb;9(1):17–26. doi: 10.1016/0143-4160(88)90034-6. [DOI] [PubMed] [Google Scholar]
- 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]
- Davies A., Simmons D. L., Hale G., Harrison R. A., Tighe H., Lachmann P. J., Waldmann H. CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cells. J Exp Med. 1989 Sep 1;170(3):637–654. doi: 10.1084/jem.170.3.637. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davies E. V., Campbell A. K., Williams B. D., Hallett M. B. Single cell imaging reveals abnormal intracellular calcium signals within rheumatoid synovial neutrophils. Br J Rheumatol. 1991 Dec;30(6):443–448. doi: 10.1093/rheumatology/30.6.443. [DOI] [PubMed] [Google Scholar]
- Davies E. V., Williams B. D., Whiston R. J., Cooper A. M., Campbell A. K., Hallett M. B. Altered Ca2+ signalling in human neutrophils from inflammatory sites. Ann Rheum Dis. 1994 Jul;53(7):446–449. doi: 10.1136/ard.53.7.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goulding N. J., Guyre P. M. Impairment of neutrophil Fc gamma receptor mediated transmembrane signalling in active rheumatoid arthritis. Ann Rheum Dis. 1992 May;51(5):594–599. doi: 10.1136/ard.51.5.594. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greenman J., Tutt A. L., George A. J., Pulford K. A., Stevenson G. T., Glennie M. J. Characterization of a new monoclonal anti-Fc gamma RII antibody, AT10, and its incorporation into a bispecific F(ab')2 derivative for recruitment of cytotoxic effectors. Mol Immunol. 1991 Nov;28(11):1243–1254. doi: 10.1016/0161-5890(91)90011-8. [DOI] [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 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]
- 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]
- Jones J., Laffafian I., Cooper A. M., Williams B. D., Morgan B. P. Expression of complement regulatory molecules and other surface markers on neutrophils from synovial fluid and blood of patients with rheumatoid arthritis. Br J Rheumatol. 1994 Aug;33(8):707–712. doi: 10.1093/rheumatology/33.8.707. [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]
- 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]
- Lund-Johansen F., Olweus J., Symington F. W., Arli A., Thompson J. S., Vilella R., Skubitz K., Horejsi V. Activation of human monocytes and granulocytes by monoclonal antibodies to glycosylphosphatidylinositol-anchored antigens. Eur J Immunol. 1993 Nov;23(11):2782–2791. doi: 10.1002/eji.1830231110. [DOI] [PubMed] [Google Scholar]
- Morgan B. P., Campbell A. K. The recovery of human polymorphonuclear leucocytes from sublytic complement attack is mediated by changes in intracellular free calcium. Biochem J. 1985 Oct 1;231(1):205–208. doi: 10.1042/bj2310205. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morgan B. P., van den Berg C. W., Davies E. V., Hallett M. B., Horejsi V. Cross-linking of CD59 and of other glycosyl phosphatidylinositol-anchored molecules on neutrophils triggers cell activation via tyrosine kinase. Eur J Immunol. 1993 Nov;23(11):2841–2850. doi: 10.1002/eji.1830231118. [DOI] [PubMed] [Google Scholar]
- Morgan B. P., van den Berg C. W., Davies E. V., Hallett M. B., Horejsi V. Cross-linking of CD59 and of other glycosyl phosphatidylinositol-anchored molecules on neutrophils triggers cell activation via tyrosine kinase. Eur J Immunol. 1993 Nov;23(11):2841–2850. doi: 10.1002/eji.1830231118. [DOI] [PubMed] [Google Scholar]
