Enhanced generation of leukotriene B4 and superoxide radical from calcium ionophore (A23187) stimulated human neutrophils after priming with interferon-alpha

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The present study was designed to investigate the effect of interferon-alpha (INF-α) on the production of leukotrienes (LTs) and superoxide radicals when intact human neutrophils were stimulated with calcium ionophore (A23187). A reverse phase high performance liquid chromatography and UV spectroscopy were employed to detect and quantitate the released LTs; namely LTC4, LTB4 and its trans isomers, 6-trans LTB4 and 12-epi-6-trans LTB4. Preincubation of intact human neutrophils at 37°C for 30 min with INF-α and stimulation with calcium ionophore A23187 for 1 min enhanced significantly the formation of LTB4. Preincubation of intact human neutrophils with INF-α and subsequent stimulation with calcium ionophore A23187 also enhanced significantly superoxide radical generation that reduced nitroblue tetrazolium into blue formazan. The in vivo effect of INF-α in rats demonstrated that the higher dose of INF-α that induced superoxide radical and LTB4 by A23187 stimulated intact human neutrophil in vitro, also induced a significant decrease in white blood cells and RBCs started at 4 h after i.p administration. The differential white blood cell count revealed that, the prime target for INF-α is the white blood cells of myeloid origin. These results might demonstrate the modulatory effects of INF-α on granulocyte functions.

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