Chemotactic 5‐Oxo‐Icosatetraenoic Acids Activate A Unique Pattern of Neutrophil Responses

Publisher Website
Google Scholar
Abstract
Neutrophil cell responses and signal pathways elicted by the chemotactic arachidonic acid metabolites (6E, 8Z, 11Z, 14Z)‐5‐oxo‐icosatetraenoic acid and (6E, 8Z, 11Z, 13E)‐5‐oxo‐15‐hydroxy‐icosatetraenoic acid were studied and compared with those of other chemotaxins. Polyphosphoinositol lipid analysis revealed activation of phosphatidylinositol‐bisphosphate 3‐kinase by both agonists. Experiments with Fura‐2 in the presence of EGTA indicated Ca2+ mobilization from intracellular stores by both 5‐oxo‐icosanoids. A transient actin response and production of small amounts of superoxide anions upon stimulation with both agents was detected. The changes induced by 5‐oxo‐icosanoids were more moderate and transient than those obtained by other chemotaxins. Desensitization studies indicated cross‐desensitization between both 5‐oxo‐icosanoids, but no interference with the response of other chemotaxins. All cell responses elicted by 5‐oxo‐icosanoids were inhibited by pertussis toxin suggesting involvement of G‐proteins, a common activation mechanism for all known potent chemotaxins. In contrast to other chemotaxins, 5‐oxo‐icosanoids at concentrations 500‐fold higher than the ED50 of other functions did not induce up‐regulation of CD11b and N‐formyl‐peptide receptors at the cell surface, and failed to potentiate N‐formyl‐peptide‐induced superoxide anion production. These results indicate that 5‐oxo‐icosanoids trigger a unique pattern of neutrophil responses.