Ischemia-Reperfusion of Rat Myocardium Activates Nuclear Factor-κB and Induces Neutrophil Infiltration Via Lipopolysaccharide-Induced CXC Chemokine

作者：Bysani Chandrasekar, Jeffrey B. Smith, Gregory L. Freeman · 发表于：Circulation · 年份：2001 · DOI：10.1161/01.cir.103.18.2296 · 被引用次数：204 · 研究领域：Cardiac Fibrosis and Remodeling、Chemokine receptors and signaling、Cardiac Ischemia and Reperfusion

BACKGROUND: Mechanisms by which neutrophils are attracted to the myocardium in ischemia/reperfusion are not fully defined. Lipopolysaccharide-induced CXC chemokine (LIX), cytokine-induced neutrophil chemoattractant (KC), and macrophage inflammatory protein-2 (MIP-2) are rodent chemokines with potent neutrophil-chemotactic activity. The goals of the present study were to evaluate the roles of these chemokines in a rat model of ischemia/reperfusion and to examine the mechanisms of chemokine induction by oxidative stress and cytokines in cultured cardiomyocytes. METHODS AND RESULTS: Male Wistar-Kyoto rats underwent 45 minutes of ligation of the left anterior descending coronary artery, followed by reperfusion for various periods. Compared with sham-operated controls, myocardium from reperfused animals had higher levels of free radicals, increased neutrophil infiltration evidenced histologically and by elevated myeloperoxidase activity, and increased nuclear factor (NF)-kappaB DNA binding activity. Ischemia-reperfusion also induced the expression of interleukin-1beta, tumor necrosis factor (TNF)-alpha, LIX, KC, and MIP-2 mRNA and protein. LIX expression was localized to resident myocardial cells, whereas KC and MIP-2 were expressed only in infiltrating inflammatory cells. Neutralization of LIX inhibited 79% of neutrophil infiltration into previously ischemic myocardium. In contrast, neutralization of KC and MIP-2 reduced neutrophil infiltration by only 28% and 37%, respectively. ...