NEUTROPHIL INDUCED OXIDATIVE INJURY OF CARDIAC MYOCYTES - A COMPARTMENTED SYSTEM REQUIRING CD11B CD18-ICAM-1 ADHERENCE
NEUTROPHIL INDUCED OXIDATIVE INJURY OF CARDIAC MYOCYTES - A COMPARTMENTED SYSTEM REQUIRING CD11B CD18-ICAM-1 ADHERENCE
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DOI：
10.1172/jci115999
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发表时间：
1992-10-01
影响因子：
15.9
通讯作者：
SMITH, CW
中科院分区：
文献类型：
--
作者：
ENTMAN, ML;YOUKER, K;SMITH, CW
我们以前已经表明，细胞因子和缺血后的心脏淋巴液诱导表达的细胞间粘附分子-1（ICAM-1，CD 54）对犬成年心肌细胞。ICAM-1表达允许活化的中性粒细胞粘附于肌细胞，其被抗CD 18 mAb R15.7或抗ICAM-1 mAb CL 18/6阻断。将白细胞介素1、肿瘤坏死因子-α或白细胞介素6刺激的心肌细胞用2 '，7'-二氯荧光素加载，并监测氧化成荧光二氯荧光素。荧光和中性粒细胞/心肌细胞粘附遵循相同的时间过程，都被阻断的单克隆抗体CD 18，CD 11b，和ICAM-1，但单克隆抗体R7.1，识别CD 11 a上的功能表位，没有抑制。铁螯合剂，去铁胺，和羟基自由基清除剂，二甲基硫脲，不抑制中性粒细胞粘附，但完全抑制荧光。与此相反，细胞外氧自由基清除剂超氧化物歧化酶和过氧化氢酶，和细胞外铁螯合剂，淀粉固定的去铁胺，不影响荧光或粘附。在所用的实验条件下，在细胞外培养基中没有检测到超氧化物的产生。荧光显微镜显示，荧光开始后5分钟内中性粒细胞粘附到一个单独的肌细胞，肌细胞挛缩迅速。荧光强度最高最初在该网站的肌细胞-中性粒细胞粘附。当仅中性粒细胞负载2 ′，7-二氯荧光素时，仅在粘附于心肌细胞的那些中性粒细胞中观察到荧光。因此，依赖于Mac-1（CD 11b/CD 18）和ICAM-1（CD 54）的粘附激活中性粒细胞呼吸爆发，导致高度分隔的铁依赖性肌细胞氧化损伤。
We have previously shown that cytokines and postischemic cardiac lymph induce expression of intercellular adhesion molecule-1 (ICAM-1, CD54) on canine adult cardiac myocytes. ICAM-1 expression allows adherence of activated neutrophils to myocytes that is blocked by anti-CD18 mAb, R15.7, or anti-ICAM-1 mAb, CL18/6. Interleukin 1, tumor necrosis factor-alpha, or interleukin 6-stimulated cardiac myocytes were loaded with 2',7'-dichlorofluorescin, and oxidation to the fluorescent dichlorofluorescein was monitored. Fluorescence and neutrophil/myocyte adherence followed the same time course, and both were blocked by monoclonal antibodies to CD18, CD11b, and ICAM-1, but mAb R7.1, recognizing a functional epitope on CD11a, was not inhibitory. The iron chelator, desferroxamine, and the hydroxyl radical scavenger, dimethylthiourea, did not inhibit neutrophil adherence, but completely inhibited fluorescence. In contrast, the extracellular oxygen radical scavengers superoxide dismutase and catalase, and the extracellular iron chelator, starch-immobilized desferroxamine, did not affect either fluorescence or adherence. Under the experimental conditions used, no superoxide production could be detected in the extracellular medium. Fluorescence microscopy demonstrated that fluorescence began within 5 min after neutrophil adherence to an individual myocyte, and myocyte contracture followed rapidly. Fluorescent intensity was highest initially at the site of myocyte-neutrophil adherence. When only neutrophils were loaded with 2',7-dichlorofluorescein, fluorescence was observed only in those neutrophils adhering to the cardiac myocytes. Thus, adherence dependent on Mac-1 (CD11b/CD18) and ICAM-1 (CD54) activates the neutrophil respiratory burst resulting in a highly compartmented iron-dependent myocyte oxidative injury.