Diverse effects of neutrophil integrin occupation on respiratory burst activation

Integrin occupation can alter the function of neutrophils (PMN), but the me chanism(s) involved is still unclear. This study demonstrated that the occu pation of PMN integrins (especially those of the beta(3) subfamily) strongl y enhances TNF stimulation of the respiratory burst but down-regulates that induced by PMA, fMLP, Con A, and serum treated zymosan. Treatment of PMN w ith genistein, staurosporine, and wortmannin, inhibitors of tyrosine kinase s, protein kinase C, and phosphotidylinostol 3-kinase (PI 3-kinase) respect ively, completely blocked the TNF-stimulated respiratory burst in PMN. Geni stein and wortmannin enhanced the PMA-stimulated respiratory burst but only in cells adherent to RGD peptide. These findings suggest that PMN integrin s (beta(3) subfamily) can generate signals that regulate the PMN agonist re sponses, probably through the activities of tyrosine kinases and PI 3-kinas e. (C) 1999 Academic Press.