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-α/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. © 1990.