EVIDENCES OF 4-HYDROXYNONENAL INVOLVEMENT IN MODULATION OF PHAGOCYTE ACTIVITIES

The peroxidative breakdown of membrane polyunsaturated fatty acids lea ds to the production or various carbonylic compounds; among these, 4-h ydroxynonenal (HNE) displays many biological properties related to neu trophil 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 mechanisms of ac tion of HNE. We observed that micromolar HNE concentrations that influ ence migration do not stimulate differently from many other chemoattra ctants the human PMN chemiluminescence (CL) induced by opsonized zymos an or phorbol 12-myristate 13-acetate (PMA). Higher HNE concentrations inhibit the light emission of stimulated PMN. Addition of 0.5 mM L-ar ginine (L-Arg), the substrate of nitric oxide synthase, into the incub ation 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 observat ions have been confirmed by electron-spin resonance (ESR) analysis. HN E, according to other stimuli, induces PMN phosphoinositide-specific p hospholipase C (PL-C). Ail these results considered together suggest t he conclusion that HNE represents an interesting endogenous molecule t hat plays a role as an inflammatory mediator involved a) in the recrui tment of phagocytic cells at the inflamed area, and b) in the modulati on of respiratory burst and of nitric oxide ((NO)-N-.) production.