Activation of Granulocytes by Anti-neutrophil Cytoplasmic Antibodies (ANCA): a Fc Gamma RII-dependent Process

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 1994 Nov 1

PMID 7955533

Citations 69

Authors

A H Mulder

P Heeringa

E Brouwer

P C Limburg

C G Kallenberg

Affiliations

Soon will be listed here.

Abstract

ANCA have been demonstrated to induce the respiratory burst in primed neutrophils. In this study we have extended the investigations on neutrophil activation by ANCA directed against proteinase 3 (PR3), myeloperoxidase (MPO) and lactoferrin (LF), and we have analysed the underlying mechanisms. All three ANCA antigens were expressed on the cell surface of primed neutrophils. Superoxide production assayed by both cytochrome c reduction and oxidation of dihydrorhodamine 123, was induced by heterologous polyclonal anti-MPO and anti-LF antibodies, and ANCA-positive plasma samples. Induction of superoxide production was dose-dependent. F(ab')2 fragments did not induce the respiratory burst. Blockade of Fc receptors by specific MoAbs showed that anti-Fc gamma RII antibodies were able to turn off the ANCA-induced respiratory burst, whereas anti-Fc gamma RIII antibodies did not. Plasma samples that induced the respiratory burst did not differ from samples that did not induce superoxide production with respect to ANCA titre, but had higher levels of the IgG3 subclass of ANCA. Levels of the other subclasses of ANCA were comparable between those samples. We conclude that ANCA-induced activation of primed neutrophils is Fc gamma RII-dependent, and appears to be facilitated by antibodies of the IgG3 subclass.

Citing Articles

Bruton's tyrosine kinase is a possible therapeutic target in microscopic polyangiitis.

Nakade I, Tamura Y, Hashimoto F, Ariza Y, Hotta S, Fujigaya H Arthritis Res Ther. 2023; 25(1):215.

PMID: 37932784 PMC: 10626711. DOI: 10.1186/s13075-023-03201-9.

Syk Activation in Circulating and Tissue Innate Immune Cells in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Prendecki M, Gulati K, Pisacano N, Pinheiro D, Bhatt T, Mawhin M Arthritis Rheumatol. 2022; 75(1):84-97.

PMID: 36428281 PMC: 10099805. DOI: 10.1002/art.42321.

Renal Expression of Annexin A1 Is Associated With the Severity of Renal Injury in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

Wang R, Wu L, Chen S, Li Z, Zhao M, Chen M Front Med (Lausanne). 2022; 9:769813.

PMID: 35783659 PMC: 9247296. DOI: 10.3389/fmed.2022.769813.

Pathogenicity of Proteinase 3-Anti-Neutrophil Cytoplasmic Antibody in Granulomatosis With Polyangiitis: Implications as Biomarker and Future Therapies.

Granel J, Korkmaz B, Nouar D, Weiss S, Jenne D, Lemoine R Front Immunol. 2021; 12:571933.

PMID: 33679731 PMC: 7930335. DOI: 10.3389/fimmu.2021.571933.

Animal Models of ANCA Associated Vasculitis.

Shochet L, Holdsworth S, Kitching A Front Immunol. 2020; 11:525.

PMID: 32373109 PMC: 7179669. DOI: 10.3389/fimmu.2020.00525.

References

Huizinga T, Kerst M, Nuyens J, Vlug A, von dem Borne A, Roos D . Binding characteristics of dimeric IgG subclass complexes to human neutrophils. J Immunol. 1989; 142(7):2359-64. View

Savage C, Gaskin G, Pusey C, Pearson J . Anti-neutrophil cytoplasm antibodies can recognize vascular endothelial cell-bound anti-neutrophil cytoplasm antibody-associated autoantigens. Exp Nephrol. 1993; 1(3):190-5. View

Tervaert J, van der Woude F, Fauci A, AMBRUS J, Velosa J, Keane W . Association between active Wegener's granulomatosis and anticytoplasmic antibodies. Arch Intern Med. 1989; 149(11):2461-5. DOI: 10.1001/archinte.149.11.2461. View

Tervaert J, Goldschmeding R, ELEMA J, VAN DER GIESSEN M, Huitema M, VAN DER HEM G . Autoantibodies against myeloid lysosomal enzymes in crescentic glomerulonephritis. Kidney Int. 1990; 37(2):799-806. DOI: 10.1038/ki.1990.48. View

Anderson C, Shen L, Eicher D, Wewers M, Gill J . Phagocytosis mediated by three distinct Fc gamma receptor classes on human leukocytes. J Exp Med. 1990; 171(4):1333-45. PMC: 2187839. DOI: 10.1084/jem.171.4.1333. View

Falk R, Terrell R, Charles L, Jennette J . Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc Natl Acad Sci U S A. 1990; 87(11):4115-9. PMC: 54058. DOI: 10.1073/pnas.87.11.4115. View

Saxon A, Shanahan F, Landers C, Ganz T, Targan S . A distinct subset of antineutrophil cytoplasmic antibodies is associated with inflammatory bowel disease. J Allergy Clin Immunol. 1990; 86(2):202-10. DOI: 10.1016/s0091-6749(05)80067-3. View

Tervaert J, Goldschmeding R, ELEMA J, Limburg P, VAN DER GIESSEN M, Huitema M . Association of autoantibodies to myeloperoxidase with different forms of vasculitis. Arthritis Rheum. 1990; 33(8):1264-72. DOI: 10.1002/art.1780330829. View

Tervaert J, Huitema M, Hene R, Sluiter W, The T, VAN DER HEM G . Prevention of relapses in Wegener's granulomatosis by treatment based on antineutrophil cytoplasmic antibody titre. Lancet. 1990; 336(8717):709-11. DOI: 10.1016/0140-6736(90)92205-v. View

10.

Fantone J . Soluble and insoluble immune complexes activate human neutrophil NADPH oxidase by distinct Fc gamma receptor-specific mechanisms. J Immunol. 1990; 145(9):3026-32. View

11.

Borregaard N, Heiple J, Simons E, Clark R . Subcellular localization of the b-cytochrome component of the human neutrophil microbicidal oxidase: translocation during activation. J Cell Biol. 1983; 97(1):52-61. PMC: 2112494. DOI: 10.1083/jcb.97.1.52. View

12.

van der Woude F, Rasmussen N, Lobatto S, Wiik A, Permin H, van Es L . Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener's granulomatosis. Lancet. 1985; 1(8426):425-9. DOI: 10.1016/s0140-6736(85)91147-x. View

13.

Falk R, Jennette J . Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis. N Engl J Med. 1988; 318(25):1651-7. DOI: 10.1056/NEJM198806233182504. View

14.

Reibman J, Haines K, 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; 146(3):988-96. View

15.

Brouwer E, Tervaert J, Horst G, Huitema M, VAN DER GIESSEN M, Limburg P . Predominance of IgG1 and IgG4 subclasses of anti-neutrophil cytoplasmic autoantibodies (ANCA) in patients with Wegener's granulomatosis and clinically related disorders. Clin Exp Immunol. 1991; 83(3):379-86. PMC: 1535341. DOI: 10.1111/j.1365-2249.1991.tb05647.x. View

16.

Jennette J, Charles L, Falk R . Antineutrophil cytoplasmic autoantibodies: disease associations, molecular biology, and pathophysiology. Int Rev Exp Pathol. 1991; 32:193-221. DOI: 10.1016/b978-0-12-364932-4.50009-5. View

17.

Hundt M, Schmidt R . The glycosylphosphatidylinositol-linked Fc gamma receptor III represents the dominant receptor structure for immune complex activation of neutrophils. Eur J Immunol. 1992; 22(3):811-6. DOI: 10.1002/eji.1830220327. View

18.

Ewert B, Jennette J, Falk R . Anti-myeloperoxidase antibodies stimulate neutrophils to damage human endothelial cells. Kidney Int. 1992; 41(2):375-83. DOI: 10.1038/ki.1992.52. View

19.

Brunkhorst B, Strohmeier G, Lazzari K, Weil G, Melnick D, Fleit H . Differential roles of Fc gamma RII and Fc gamma RIII in immune complex stimulation of human neutrophils. J Biol Chem. 1992; 267(29):20659-66. View

20.

Keogan M, Esnault V, Green A, Lockwood C, Brown D . Activation of normal neutrophils by anti-neutrophil cytoplasm antibodies. Clin Exp Immunol. 1992; 90(2):228-34. PMC: 1554613. DOI: 10.1111/j.1365-2249.1992.tb07934.x. View