ANTINEUTROPHIL 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 hypoth esis that the T cell inflammatory response causing the vasculitis in W egener's granulomatosis (WG) is secondary to stimulation of neutrophil s by ANCA So far there is no evidence for a direct effect of ANCA on l ymphocytes. The present study was designed to examine whether lymphocy tes can be directly stimulated by ANCA to adhere to endothelial extrac ellular matrix (ECM) proteins. Human and mouse ANCA-enriched IgG were tested for their ability to increase adhesion of human T lymphocytes t o fibronectin, laminin, and intact ECM. Incubation of human T lymphocy tes with human ANCA-enriched IgQ increased adhesion of the lymphocytes in a dose dependent manner to fibronectin, laminin, and intact ECM (t he 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 t o fibronectin, laminin, and intact ECM: was observed when the cells we re incubated with the F(ab)(2) fragment of ANCA-enriched IgG, Similarl y, ANCA enriched IgG produced in mice increased the adhesion of lympho cytes to fibronectin (the percentage adhesion to fibronectin was 29.7 +/- 4.3 and 16.6 +/- 1.9% for lymphocytes incubated with mouse IgGr-AN CA or control mouse IgG, respectively; P = 0.0008). These results may suggest that ANCA can directly stimulate lymphocytes to adhere to endo thelial ECM and to induce the vasculitic lesions of WG. It remains to be shown by which mechanisms ANCA stimulate lymphocytes to adhere to E CM. (C) 1997 Academic Press.