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  • Title: Chemotactic 5-oxo-icosatetraenoic acids activate a unique pattern of neutrophil responses. Analysis of phospholipid metabolism, intracellular Ca2+ transients, actin reorganization, superoxide-anion production and receptor up-regulation.
    Author: Norgauer J, Barbisch M, Czech W, Pareigis J, Schwenk U, Schröder JM.
    Journal: Eur J Biochem; 1996 Mar 15; 236(3):1003-9. PubMed ID: 8665888.
    Abstract:
    Neutrophil cell responses and signal pathways elicited 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-biphosphate 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 elicited by 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.
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