Effect of 4-hydroxynonenal on superoxide anion production from primed human neutrophils

HNE (4-hydroxy-2,3-trans-nonenal), and aldehydic product of lipid peroxidation, has been reported to modulate different functional parameters of human and rat neutrophils (PMNs), such as chemiluminescence, migration and some enzymatic activities, thus exerting effects that varied according to the concentration tested. Experiments were done to evaluate the effects of HNE on superoxide anion (O2-) production from human PMNs, isolated from healthy volunteers. After having tested that HNE by itself was not able to activate the cells, comparisons were made between its effects on PMNs, stimulated by either a single stimulus, N-formyl-methionyl-leucyl-phenylalanine (FMLP), or a combination of stimuli, such as FMLP and the neuropeptide substance P (SP; primed PMNs). In the concentration range tested (10(-12) - 10(-4) M), HNE inhibited FMLP-evoked O2- production with an IC50 of 11.6 +/- 1.5 x 10(-6) M; at concentrations < or = 10(-6) M, HNE enhanced O2- production elicited by FMLP + SP, while higher concentrations were inhibitory. There was a bell-shaped dose-response curve to the enhancing effects of HNE, depending on the incubation time being recorded after only short periods (< or = 5 min) of the exposure of the cells to HNE; this was not shown by structurally-related aldehydes, such as 2-nonenal and nonanal. These results suggest that low concentrations of HNE may participate in the evolution of the inflammatory process, by contributing to the activation of PMNs. The effects of high concentrations of the aldehyde may represent a mechanism which contributes to the regulation of the extent of the inflammatory response.