Gruber D F, O'Halloran K P, Farese A M
Experimental Hematology Department, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20814-5145.
J Biol Response Mod. 1989 Oct;8(5):462-7.
Oxygen-derived free radicals are believed to contribute to reperfusion injury based, in part, upon results conferred by the pharmacologic administration of allopurinol. Allopurinol inhibits xanthine oxidase (XO) activity in ischemic tissues. The possible role of XO as a pathologic mediator prompted examination of its effects on isolated peripheral canine neutrophils. In contrast to neutrophils alone, or following stimulation with phorbol myristate acetate (PMA), it was determined that XO affected both the membrane potential and the metabolism significantly. Membrane potential assay showed that at 5-10 min, PMA depolarized 89-96% of the canine neutrophils between 32-48%. Incubation with 0.5 U/ml XO involved fewer cells (54-86%), but at substantially increased cellular depolarization levels (76-90%). Metabolic assay showed that XO concentrations as low as 0.124 U induced significant cellular H2O2 production compared with temperature controls. At 0.25-0.5 U XO/10(6) cells, cytosolic H2O2 increases were almost three times those of PMA.
基于别嘌呤醇药物给药所产生的结果，人们认为氧衍生的自由基在一定程度上导致了再灌注损伤。别嘌呤醇可抑制缺血组织中的黄嘌呤氧化酶（XO）活性。XO作为病理介质的可能作用促使人们研究其对分离的犬外周血中性粒细胞的影响。与单独的中性粒细胞或用佛波酯（PMA）刺激后的中性粒细胞相比，已确定XO对膜电位和代谢均有显著影响。膜电位测定表明，在5 - 10分钟时，PMA使89 - 96%的犬中性粒细胞去极化32 - 48%。用0.5 U/ml XO孵育涉及的细胞较少（54 - 86%），但细胞去极化水平显著增加（76 - 90%）。代谢测定表明，与温度对照相比，低至0.124 U的XO浓度即可诱导细胞产生显著的H2O2。在0.25 - 0.5 U XO/10(6)细胞时，胞质H2O2的增加几乎是PMA的三倍。
