Effect of inhibitors of distinct signalling pathways on neutrophil Q2- 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-alpha (TNF), or antibodies against the common beta 2 chain of leukocyte integrins (CD18), or LFA-1 (CD11a) 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.
Laudanna
C
C
Institute of General Pathology, University of Verona, Italy.
Rossi
F
F
Berton
G
G
D000470:Alkaloids / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D015703:Antigens, CD / Q000502:physiology*; D018821:CD18 Antigens; D019833:Genistein; D016023:Integrins / Q000502:physiology*; D007529:Isoflavones / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D016897:Respiratory Burst / Q000187:drug effects*; D015398:Signal Transduction; D019311:Staurosporine; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000077191:Wortmannin
D000470:Alkaloids; D000730:Androstadienes; D015703:Antigens, CD; D018821:CD18 Antigens; D016023:Integrins; D007529:Isoflavones; D016169:Lymphocyte Function-Associated Antigen-1; D014409:Tumor Necrosis Factor-alpha; D010566:Virulence Factors, Bordetella; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019833:Genistein; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D000077191:Wortmannin