The role of 5-hydroperoxyeicosatetraenoic acid in neutrophil activation.

5-Hydroperoxyeicosatetraenoic acid (5HPETE) has been recently reported to play an important role in regulating and modulating neutrophil function. In order to clarify the mechanism of neutrophil activation by 5HPETE, we have measured the cytosolic free calcium, which is thought to be necessary for neutrophil activation using fura-2-loaded human neutrophils. Low concentration of 5HPETE, which is thought to be produced during cell activation, had minimal effect on cytosolic free calcium by itself but dose-dependently augmented FMLP-stimulated increase in cytosolic free calcium in the presence or absence of extracellular calcium without converting to LTB4. 5HPETE had no effect on 3H-FMLP binding to human neutrophils. The present data suggested that 5HPETE would augment FMLP-stimulated increase in cytosolic free calcium by enhancing the influx of extracellular calcium and/or the release of calcium from intracellular pool, which resulted in augmentation of neutrophil activation by primary agonist such as FMLP.