ACTIVATION OF PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE-C OF RAT NEUTROPHILS BY THE CHEMOTACTIC ALDEHYDES 4-HYDROXY-2,3-TRANS-NONENAL AND 4-HYDROXY-2,3-TRANS-OCTENAL

A comparison has been made between the effects of 4-hydroxy-2,3-trans- nonenal (HNE) and 4-hydroxy-2,3-trans-octenal (HOE), two lipid peroxid ation products, on the basal and GTPgammaS-stimulated activities of ph osphoinositide-specific phospholipase C (PL-C) of rat polymorphonuclea r leukocytes. PL-C activity was determined in vitro by measuring the h ydrolysis of [H-3] phosphatidylinositol-4,5-bis-phosphate (PtdIns-P-2) added as exogenous substrate to neutrophil plasma membranes. PL-C was activated by concentrations of HNE ranging from 10(-8) to 10(-6) M bo th in the presence and in the absence of 2 x 10(-5) M GTPgammaS; HOE s timulated the enzymatic activity between 10(-11) and 10(-8) M; maximal stimulation was given by 10(-11) M HOE plus GTPgammaS. The aldehyde c oncentrations able to accelerate PtdIns-P-2 breakdown displayed a good correspondence with those which have been reported to stimulate the o riented migration pf rat neutrophils. Pretreatment of neutrophils with pertussis toxin prevented the stimulation of PL-C by 10(-11) M HOE an d by HOE plus GTPgammaS. Our results suggest that the chemotactic acti on of HNE and HOE might depend on the activation of PL-C; furthermore a regulatory G protein appears to be involved in the acceleration of P tdIns-P-2 turnover by HOE.