: Enhanced generation of leukotriene B-4 and superoxide radical from calcium ionophore (A23187) stimulated human neutrophils after priming with interferon-alpha.

Abstract

The present study was designed to investigate the effect of interferon-alpha ( INF-alpha) 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 degreesC for 30 min with INF-alpha and stimulation with calcium ionophore A23187 for 1 min enhanced significantly the formation of LTB4. Preincubation of intact human neutrophils with INF-alpha 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-alpha in rats demonstrated that the higher dose of INF-alpha 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-alpha is the white blood cells of myeloid origin. These results might demonstrate the modulatory effects of INF-alpha, on granulocyte functions.