CIRCULATING LEUKOCYTE INTEGRIN EXPRESSION IN WEGENERS GRANULOMATOSIS

Leukocyte adhesion and infiltration are important in the pathogenesis of Wegener's granulomatosis (WG). We tested the hypothesis that the ex pression of the beta 1-chain integrin VLA-4 (CD49d/CD29) and the beta 2-chain integrins LFA-1 (CD11a/CD18), Mac-1 (CD11a/ CD18), and gp150,9 5 (CD11c/CD18) is increased on leukocytes in patients with active WG. Fifteen patients with active WG as defined by positive antineutrophil cytoplasmic autoantibody (cANCA) titers and biopsy, 30 patients with W G in remission as defined by negative cANCA titers and/or immunosuppre ssive therapy, 25 normal control subjects, and 12 patients with other inflammatory renal and systemic diseases were studied. Surface express ion of LFA-1, Mac-1, p150, 95, and VLA-4 on neutrophils, lymphocytes, and monocytes was measured by fluorescent antibody cell sorting with m onoclonal antibodies against CD11a, CD11b, CD11c, CD18, CD49d, and CD2 9 respectively. Immunocytochemistry and confocal microscopy were also utilized. beta 1 (CD29) and beta 2 (CD18) integrin subunit expression on neutrophils, monocytes, and lymphocytes from patients with acute WG was significantly increased compared with healthy persons and compare d with patients with treated vasculitis. Furthermore, the a-integrin s ubunit CD11b expression was increased on granulocytes and monocytes, b ut not on lymphocytes. Finally, the alpha-integrin subunit CD11a expre ssion was increased on monocytes. Immunocytochemistry showed that the increased immunoreactivity on neutrophils was evenly distributed on th e plasma membrane and in the cytosol. Immunosuppression resulted in de creased expression of the beta 1 and beta 2-integrin subunits. It was concluded that the integrin adhesion molecules, particularly Mac-1 (CD 11b/CD18), are upregulated on leukocytes in active WG. This finding su ggests a role for integrin expression in the pathogenesis of WG and a possible clue for treatment.