Enhanced generation of leukotriene B4 and superoxide radical from calcium ionophore (A23187) stimulated human neutrophils after priming with interferon-alpha.
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 degrees C 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.
Al-Shabanah
O A
OA
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Mansour
M A
MA
Elmazar
M M
MM
D000818:Animals; D001772:Blood Cell Count; D000001:Calcimycin / Q000494:pharmacology; D004909:Erythrocyte Indices; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013481:Superoxides / Q000378:metabolism*
D016898:Interferon-alpha; D007476:Ionophores; D013481:Superoxides; D007975:Leukotriene B4; D000001:Calcimycin