ROLE OF INFLAMMATION IN EARLY MYOCARDIAL ISCHEMIA

我们计划项目赠款的总体目标是描述 介导强烈炎症反应的细胞和分子事件 在先前的缺血再灌流后迅速发生的反应 心肌。这种炎症反应是一种典型的 损伤和大量证据表明，它可能会延长心脏 受伤。本计划项目资助的三个项目均为 旨在描述控制细胞和分子事件的特征 黏附分子的诱导、表达、激活和黏附 分子介导的细胞事件。黏附分子支配和控制 白细胞转运、白细胞分泌与白细胞损伤 而对它们的新陈代谢的了解对于 对创伤后炎症反应的认识 再灌流。项目1利用了一种慢性脑缺血动物模型 心脏淋巴管可以插入再灌流以允许 不存在心脏细胞外液的动物获得心脏细胞外液的途径 外科创伤。粘连的作用、诱导和激活 分子的研究是通过测量白细胞流量，免疫- 细胞化学、原位杂交和定量Northern杂交。 项目2利用了一种新开发的小鼠缺血模型 和再灌流，旨在研究遗传的后果 删除特定的黏附分子、趋化剂和 趋化受体。基因的分子和细胞后果 对删除进行了研究。项目3涉及细胞和分子 单个黏附分子控制白细胞的机制 运输、白细胞分泌和白细胞引起的心脏损伤。

The overall objective of our Program Project Grant is to characterize the cellular and molecular events which mediate the intense inflammatory response that occurs rapidly upon reperfusion of the previously ischemic myocardium. This inflammatory response represents a classic reaction to injury and substantial evidence suggests that it may extend cardiac injury. The three projects of this Program Project Grant all are directed at characterizing the cellular and molecular events that control adhesion molecule induction, expression, activation, and adhesion molecule mediated cellular events. Adhesion molecules govern and control leukocyte trafficking, leukocyte secretion and leukocyte mediated injury and the understanding of their metabolism is critical to the understanding of the inflammatory reaction to injury ensuing from reperfusion. Project 1 utilizes a chronic animal model of ischemia and reperfusion in which the cardiac lymph duct can be cannulated to allow access to cardiac extracellular fluid in animals in whom there is no surgical trauma. The role, induction, and activation of adhesion molecules is studied by measurements of leukocyte flux, immuno- cytochemistry, in situ hybridization, and quantitative Northern blotting. Project 2 takes advantage of a newly developed mouse model of ischemia and reperfusion and is designed to study the consequence of genetic deletion of specific adhesion molecules, chemotactic agents and chemotactic receptors. Molecular and cellular consequences of gene deletion are studied. Project 3 deals with the cellular and molecular mechanisms by which individual adhesion molecules control leukocyte trafficking, leukocyte secretion, and leukocyte induced cardiac injury.