INTERLEUKIN-8 GENE INDUCTION IN THE MYOCARDIUM AFTER ISCHEMIA AND REPERFUSION IN-VIVO
INTERLEUKIN-8 GENE INDUCTION IN THE MYOCARDIUM AFTER ISCHEMIA AND REPERFUSION IN-VIVO
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DOI：
10.1172/jci117680
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发表时间：
1995-01-01
影响因子：
15.9
通讯作者：
ENTMAN, ML
中科院分区：
文献类型：
--
作者：
KUKIELKA, GL;SMITH, CW;ENTMAN, ML
心肌细胞的神经元粘附和直接细胞毒性需要趋化刺激，并依赖于CD 18-ICAM-1结合。为了研究IL-8在这种相互作用中的作用，我们克隆了犬IL-8 cDNA，并在大肠杆菌BL 21细胞中表达了成熟的重组蛋白。重组犬IL-8能显著增加中性粒细胞与离体犬心肌细胞的粘附。这种粘附导致对心肌细胞的直接细胞毒性。这两个过程被特异性地阻断针对CD 18和IL-8的抗体。在体内，在冠状动脉闭塞1小时后，IL-8 mRNA在心肌再灌注段中被显著且一致地诱导。IL-8 mRNA在正常灌注的心肌节段中不被诱导，在缺血3或4 h后检测到少量的IL-8 mRNA，在大多数缺血心肌节段中诱导水平最高，IL-8 mRNA在再灌注的前3 h达到峰值，并持续高水平超过24 h。IL-8染色存在于坏死和存活心肌之间的边界附近的炎性浸润中，以及在同一区域的小静脉中。这些发现提供了第一个直接证据，在缺血和再灌注犬心肌IL-8的调节，并支持假设，IL-8参与嗜中性粒细胞介导的心肌损伤。
Neutrophil adhesion and direct cytotoxicity for cardiac myocytes require chemotactic stimulation and are dependent upon CD18-ICAM-1 binding. To characterize the potential role of IL-8 in this interaction, canine IL-8 cDNA was cloned and the mature recombinant protein expressed in Escherichia coli BL21 cells, Recombinant canine IL-8 markedly increased adhesion of neutrophils to isolated canine cardiac myocytes. This adhesion resulted in direct cytotoxicity for cardiac myocytes. Both processes were specifically blocked by antibodies directed against CD18 and IL-8, In vivo, after 1 h of coronary occlusion, IL-8 mRNA was markedly and consistently induced in reperfused segments of myocardium. IL-8 mRNA was not induced in control (normally perfused) myocardial segments, Minimal amounts of IL-8 mRNA were detected after 3 or 4 h of ischemia without reperfusion, Highest levels of induction were evident in the most ischemic myocardial segments, IL-8 mRNA peaked in the first 3 h of reperfusion and persisted at high levels beyond 24 h. IL-8 staining was present in the inflammatory infiltrate near the border between necrotic and viable myocardium, as well as in small veins in the same area. These findings provide the first direct evidence for regulation of IL-8 in ischemic and reperfused canine myocardium and support the hypothesis that IL-8 participates in neutrophil-mediated myocardial injury.