EFFECT OF INHIBITORS OF DISTINCT SIGNALING PATHWAYS ON NEUTROPHIL O2- GENERATION IN RESPONSE TO TUMOR-NECROSIS-FACTOR-ALPHA, AND ANTIBODIES AGAINST CD18 AND CD11A - EVIDENCE FOR A COMMON AND UNIQUE PATTERN OF SENSITIVITY TO WORTMANNIN AND PROTEIN TYROSINE KINASE INHIBITORS

In these studies we show that stimulation of O2- generation by Tumor necrosis factor-α (TNF), or antibodies against the common β2 chain of leukocyte integrins (CD 18), or LFA-1 (CD 11 a) displays a common and unique pattern of sensitivity or insensitivity to inhibitors of different signalling pathways. Both ways of stimulating neutrophil O2- generation were blocked by wortmannin, an inhibitor of myosin light chain kinase (Nakanishi, S.,et al.,1992.,J. Biol. Chem. 267, 2157-2163), and three different inhibitors of protein tyrosine kinases. Neither staurosporine, a protein kinase C inhibitor, nor Pertussis toxin, at concentrations which inhibited O2- generation in response to PMA, and FMLP. respectively, had any effect. © 1993 Academic Press. All rights reserved.