Experimental studies on the mechanism of action of 4-Hydroxy-2,3-trans-nonenal, a lipid peroxidation product displaying chemotactic activity toward rat neutrophils

Abstract

The effects of 4‐hydroxy‐2,3‐trans‐nonenal (HNE) and nonanal on the activity of phosphoinositide‐specific phospholipase C of rat neutrophils have been studied in parallel with their action on neutrophil oriented migration. Concentrations of HNE ranging from 10⁻⁷ to 10⁻⁵M significantly stimulated the oriented migration of rat polymorphonuclear leukocytes. HNE stimulated both the basal and GTP gamma S‐induced phospholipase C activity when used at concentrations between 10⁻⁸ and 10⁻⁶M. Nonanal was devoid both of chemotactic activity and of any action on phospholipase C activity. The effect of GTP gamma S on the stimulation of phospholipase C induced by HNE was higher when the lowest dose of the aldehyde was used; the finding of an additive effect between 10⁻⁸M HNE and 2 × 10⁻⁵M GTP gamma S suggests that the two compounds may share a final common pathway of action. These results suggest that the chemotactic activity of HNE might be mediated, like that of other more well‐known chemoattractants, by the stimulation of phosphoinositide‐specific phospholipase C.