Tumor necrosis factor-alpha/cachectin activates the O2(-)-generating system of human neutrophils independently of the hydrolysis of phosphoinositides and the release of arachidonic acid.
We have investigated the mechanisms of transmembrane signalling implicated in the activation of the respiratory burst of adherent neutrophils by tumor necrosis factor-alpha/cachectin (TNF). The activation of the respiratory burst by TNF is insensitive to pertussis toxin and weakly sensitive to protein kinase C inhibitors. Cytochalasin B and dibutyryl cyclic AMP have an inhibitory effect. The activation of the respiratory burst by TNF takes place in the absence of formation of 3H-inositol phosphates, 32P-phosphatidic acid, and 3H-arachidonic acid. These results demonstrate that the activation of the respiratory burst by an endogenous, physiologic stimulus can be independent of the formation of messengers derived from hydrolysis of phosphoinositides.
Laudanna
C
C
Institute of General Pathology, University of Verona, Italy.
Miron
S
S
Berton
G
G
Rossi
F
F
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D001095:Arachidonic Acids / Q000097:blood*; D003994:Bucladesine / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000097:blood*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D010712:Phosphatidic Acids / Q000097:blood; D010716:Phosphatidylinositols / Q000097:blood*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D019311:Staurosporine; D013481:Superoxides / Q000097:blood*; D013806:Theophylline / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000470:Alkaloids; D001095:Arachidonic Acids; D007295:Inositol Phosphates; D007546:Isoquinolines; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D010566:Virulence Factors, Bordetella; D013481:Superoxides; D003994:Bucladesine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D013806:Theophylline; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019311:Staurosporine