Anti-neutrophil cytoplasmic antibody-enriched IgG induces adhesion of human T lymphocytes to extracellular matrix proteins.
Recent studies have shown that anti-neutrophil cytoplasmic antibodies (ANCA) can activate neutrophils to adhere to endothelium, degranulate, and cause endothelial cell injury. These data have lead to the hypothesis that the T cell inflammatory response causing the vasculitis in Wegener's granulomatosis (WG) is secondary to stimulation of neutrophils by ANCA. So far there is no evidence for a direct effect of ANCA on lymphocytes. The present study was designed to examine whether lymphocytes can be directly stimulated by ANCA to adhere to endothelial extracellular matrix (ECM) proteins. Human and mouse ANCA-enriched IgG were tested for their ability to increase adhesion of human T lymphocytes to fibronectin, laminin, and intact ECM. Incubation of human T lymphocytes with human ANCA-enriched IgG increased adhesion of the lymphocytes in a dose-dependent manner to fibronectin, laminin, and intact ECM (the percentage adhesion to intact ECM was 55.7 +/- 3.1 and 45.0 +/- 1.0% for lymphocytes incubated with human IgG containing ANCA or control human IgG, respectively; P = 0.0045). The same induction of adhesion to fibronectin, laminin, and intact ECM was observed when the cells were incubated with the F(ab)2 fragment of ANCA-enriched IgG. Similarly, ANCA-enriched IgG produced in mice increased the adhesion of lymphocytes to fibronectin (the percentage adhesion to fibronectin was 29.7 +/- 4.3 and 16.6 +/- 1.9% for lymphocytes incubated with mouse IgG-ANCA or control mouse IgG, respectively; P = 0.0008). These results may suggest that ANCA can directly stimulate lymphocytes to adhere to endothelial ECM and to induce the vasculitic lesions of WG. It remains to be shown by which mechanisms ANCA stimulate lymphocytes to adhere to ECM.
Tomer
Y
Y
Department of Medicine B', Sheba Medical Center, Tel-Hashomer, Israel.
Lider
O
O
Gilburd
B
B
Hershkoviz
R
R
Meroni
P L
PL
Wiik
A
A
Shoenfeld
Y
Y
D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000494:pharmacology*; D002448:Cell Adhesion / Q000276:immunology; D004727:Endothelium / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D014890:Granulomatosis with Polyangiitis / Q000097:blood / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D013601:T-Lymphocytes / Q000166:cytology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D000939:Epitopes; D016326:Extracellular Matrix Proteins; D007074:Immunoglobulin G