Role of leukocytes during ischemiareperfusion

Ischemic hypoxia induces an inflammatory reaction and activates polymorphonuclear leukocytes (PMN's) by pro-inflammatory mediators. PMN's then adhere to the micro-vascular endothelium by means of adhesion molecules, a process mediated largely via CD11a/CD18 and CD11b/CD18 interactions with intercellular adhesion molecule-1. PMN's are required for necrotic debris removal after severe ischemia. The cascade of diapedesis is orchestered by these adhesion molecules (selectins, integrins), cytokines and NO. The ensuing tissue damage is no longer limited to free radicals but also by proteolytic enzymes released by PMN's (elastases, collagenases, gelatinases) activated by HOCl. Importantly, proteolytic enzymes demonstrate a much longer activity than free radicals, partially explained by the neutralization effect of free radicals on the anti-proteases shield.

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