Ikeda U, Ikeda M, Kano S, Shimada K
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
J Cardiovasc Pharmacol. 1994 Apr;23(4):647-52. doi: 10.1097/00005344-199404000-00019.
Cytokine induction of intercellular adhesion molecule-1 (ICAM-1) in cardiac myocytes may be a critical step in inflammation associated with ischemia-reperfusion injury. We investigated the involvement of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and interleukin 8 (IL-8) on neutrophil-myocyte adhesion; These cytokines are increased in plasma of patients with acute myocardial infarction (AMI). ICAM-1 expression on cultured neonatal rat cardiac myocytes was determined through immunohistochemical and enzyme-linked immunosorbent assay (ELISA) analysis. ICAM-1 mRNA expression in myocytes was investigated by Northern blot hybridization. Rat neutrophils isolated from peripheral blood (PB) were used for adherence assay. In immunohistochemical study, cultured neonatal rat cardiac myocytes constitutively expressed ICAM-1 molecules. In ELISA analysis, ICAM-1 molecule expression on myocytes was significantly stimulated by TNF-alpha (100 U/ml), but not by IL-6 (100 U/ml) or IL-8 (100 ng/ml) dose dependently. The effect of TNF-alpha was observed as early as 6 h after stimulation. Levels of ICAM-1 mRNA were very low or almost undetectable in unstimulated myocytes, but its expression was markedly induced after exposure to TNF-alpha for 3 h. IL-6 and IL-8 showed no effect on ICAM-1 mRNA accumulation. Adhesion of rat neutrophils to myocytes was stimulated by TNF-alpha, and the effect of TNF-alpha on adherence was significantly inhibited by an anti-ICAM-1 monoclonal antibody (MoAb). These results show that TNF-alpha, but not IL-6 and IL-8, promotes neutrophil-myocyte adhesion through ICAM-1 expression, suggesting involvement of TNF-alpha in inflammation associated with ischemia-reperfusion injury.
细胞因子诱导心肌细胞表达细胞间黏附分子-1（ICAM-1）可能是与缺血再灌注损伤相关炎症中的关键步骤。我们研究了肿瘤坏死因子-α（TNF-α）、白细胞介素6（IL-6）和白细胞介素8（IL-8）在中性粒细胞与心肌细胞黏附中的作用；这些细胞因子在急性心肌梗死（AMI）患者血浆中水平升高。通过免疫组织化学和酶联免疫吸附测定（ELISA）分析来确定培养的新生大鼠心肌细胞上ICAM-1的表达。通过Northern印迹杂交研究心肌细胞中ICAM-1 mRNA的表达。从外周血（PB）分离的大鼠中性粒细胞用于黏附试验。在免疫组织化学研究中，培养的新生大鼠心肌细胞组成性表达ICAM-1分子。在ELISA分析中，TNF-α（100 U/ml）能显著刺激心肌细胞上ICAM-1分子的表达，而IL-6（100 U/ml）或IL-8（100 ng/ml）则无此剂量依赖性刺激作用。TNF-α的作用在刺激后6小时即可观察到。未刺激的心肌细胞中ICAM-1 mRNA水平非常低或几乎检测不到，但在暴露于TNF-α 3小时后其表达明显诱导。IL-6和IL-8对ICAM-1 mRNA积累无影响。TNF-α刺激大鼠中性粒细胞与心肌细胞的黏附，抗ICAM-1单克隆抗体（MoAb）可显著抑制TNF-α对黏附的作用。这些结果表明，TNF-α而非IL-6和IL-8通过ICAM-1表达促进中性粒细胞与心肌细胞黏附，提示TNF-α参与了与缺血再灌注损伤相关的炎症反应。
