Evidences of 4-hydroxynonenal involvement in modulation of phagocyte activities.

The peroxidative breakdown of membrane polyunsaturated fatty acids leads to the production of various carbonylic compounds: among these, 4-hydroxynonenal (HNE) displays many biological properties related to neutrophil functions. It stimulates rat and human polymorphonuclear (PMN) cell migration and has been detected during inflammation. The aim of this study was to elucidate and well characterize the mechanism of action of HNE. We observed that micromolar HNE concentrations that influence migration do not stimulate differently from many other chemoattractants the human PMN chemiluminescence (CL) induced by opsonized zymosan or phorbol 12-myristate 13-acetate (PMA). Higher HNE concentrations inhibit the light emission of stimulated PMN. Addition of 0.5 mM L-arginine (L-arg), the substrate of nitric oxide synthase, into the incubation medium had the effect of modifying human CL. In fact, HNE at 10-6 M, a concentration which is ineffective in absence of L-Arg, at 10-5 M reduces CL emission of PMA-stimulated human PMN. These observations have been confirmed by electron-spin resonance (ESR) analysis. HNE, according to other stimuli, induced PMN phosphoinositide-specific phospholipase C (PL-C). All these results considered together suggest the conclusion that HNE represents an interesting endogenous molecule that plays a role as an inflammatory mediator involved a) in the recruitment of phagocytic cells at the inflamed area, and b) in the modulation of respiratory burst and of nitric oxide (NO) production.