Ma X L, Tsao P S, Viehman G E, Lefer A M
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pa. 19107.
Circ Res. 1991 Jul;69(1):95-106. doi: 10.1161/01.res.69.1.95.
We investigated the interaction between activated cat polymorphonuclear neutrophils (PMNs) and coronary vascular endothelial cells in vitro. It was shown that 1) 90 minutes of low-flow perfusion without reperfusion had no deleterious effects on endothelium-dependent vasodilation, whereas 90 minutes of low-flow perfusion and 20 minutes of reperfusion with a blood cell-free solution induced a 20-25% endothelial dysfunction; 2) activated PMNs produced endothelium-dependent vasoconstriction in coronary artery rings isolated from cat hearts undergoing 90 minutes of low-flow perfusion and 20 minutes of reperfusion with a blood cell-free Krebs-Henseleit solution; 3) addition of the superoxide free radical scavenger, superoxide dismutase (150 micrograms/ml), or an antibody directed against CD18 of PMN adherence glycoprotein complex (MAbR15.7, 20 micrograms/ml) attenuated PMN-induced vasoconstriction significantly, but addition of a hydroxyl radical scavenger [N-(2-mercaptopropionyl)-glycine, 150 micrograms/ml], a cyclooxygenase inhibitor, or a lipoxygenase inhibitor had no protective effect; 4) exposure of rings to a superoxide radical-generating system (i.e., xanthine and xanthine oxidase) produced significant vasoconstriction that was similar to that observed with activated PMNs and was inhibited by superoxide dismutase; and 5) activated PMNs produced a marked coronary endothelial dysfunction characterized by a decreased response to the endothelium-dependent vasodilators acetylcholine and A23187. Addition of either superoxide dismutase or MAbR15.7 protected against endothelial dysfunction. These results indicate that activated PMNs produce significant vasoconstriction and endothelial dysfunction in coronary arteries isolated from low-flow perfusion-reperfused hearts. These effects appear to be mediated primarily by superoxide radicals generated by activated PMNs that either inactivate or inhibit the synthesis and release of endothelium-derived relaxing factor. We conclude that activated PMNs are able to induce endothelial dysfunction by releasing free radicals and possibly other substances.
我们在体外研究了活化的猫多形核中性粒细胞（PMN）与冠状动脉血管内皮细胞之间的相互作用。结果表明：1）90分钟的低流量灌注且无再灌注对内皮依赖性血管舒张无有害影响，而90分钟的低流量灌注并用无血细胞溶液再灌注20分钟则导致20%-25%的内皮功能障碍；2）活化的PMN在从经历90分钟低流量灌注并用无血细胞的Krebs-Henseleit溶液再灌注20分钟的猫心脏分离出的冠状动脉环中产生内皮依赖性血管收缩；3）添加超氧阴离子自由基清除剂超氧化物歧化酶（150微克/毫升）或针对PMN黏附糖蛋白复合物CD18的抗体（单克隆抗体R15.7，20微克/毫升）可显著减弱PMN诱导的血管收缩，但添加羟自由基清除剂[N-（2-巯基丙酰基）-甘氨酸，150微克/毫升]、环氧化酶抑制剂或脂氧合酶抑制剂则无保护作用；4）将血管环暴露于超氧阴离子生成系统（即黄嘌呤和黄嘌呤氧化酶）会产生显著的血管收缩，这与活化的PMN所观察到的相似，且被超氧化物歧化酶抑制；5）活化的PMN产生明显的冠状动脉内皮功能障碍，其特征是对内皮依赖性血管舒张剂乙酰胆碱和A23187的反应降低。添加超氧化物歧化酶或单克隆抗体R15.7可预防内皮功能障碍。这些结果表明，活化的PMN在从低流量灌注-再灌注心脏分离出的冠状动脉中产生显著的血管收缩和内皮功能障碍。这些作用似乎主要由活化的PMN产生的超氧阴离子自由基介导，这些自由基使内皮衍生的舒张因子失活或抑制其合成与释放。我们得出结论，活化的PMN能够通过释放自由基以及可能的其他物质诱导内皮功能障碍。
