UP-REGULATION OF THE GRANULOCYTE ADHESION MOLECULE MAC-1 BY AUTOANTIBODIES IN AUTOIMMUNE VASCULITIS

The characteristic finding of autoantibodies in patients with vasculit is has raised the possibility that these antibodies play a role in the pathogenesis of the disease. The expression of adhesion molecules (AM ) on leucocytes and endothelial cells is believed to be integral to th e development of vasculitis. We therefore investigated the effect of s era, positive for anti-neutrophil cytoplasmic antibodies (ANCA) or ant i-nuclear antibodies (ANA) from patients with vasculitis, on granulocy te expression of the adhesion molecule Mac-1 (CD11b). Autoantibody-pos itive sera from 15 out of 35 patients with vasculitis stimulated an up -regulation of Mac-1 on granulocytes. In most cases this effect was re produced by the autoantibody-positive purified IgG fraction. Autoantib ody-negative samples did not stimulate AM up-regulation. Of interest, preincubation of sera with purified antigens did not inhibit AM up-reg ulation by the autoantibody samples. Blocking the Fc receptors on gran ulocytes did result in a decrease of Mac-1 up-regulation, but this tre nd was not statistically significant. These results suggest that both ANCA and ANA have the capacity to up-regulate granulocyte AM expressio n, and that while Fc interaction with granulocyte Fc receptors is impo rtant, it is not the only mechanism whereby such autoantibodies activa te cells.