The role of leukocytes in tissue injury.

The recruitment of leukocytes to the sites of inflammation and leukocyte-derived inflammatory mediators contributes to the development of tissue injury associated with inflammatory diseases. The first step in the pathogenesis of inflammatory conditions is adhesion of circulating leukocytes to activated vascular endothelial cell in the inflamed tissues and subsequent transmigration through the endothelial cells. During these processes, leukocytes are activated to secrete a variety of substances such as growth factors, chemokines and cytokines, complement components, proteases, nitric oxide, and reactive oxygen metabolites, which are considered to be one of the primary sources of the tissue injury. Prevention or reduction of leukocyte-endothelial cell adhesion often results in a profound attenuation of the microvasculature and parenchymal cell dysfunction in various animal models of human inflammatory diseases. It has been shown that all aspirin-like non-steroidal anti-inflammatory agents share at least one characteristic in that all of these agents diminish the adhesive interactions required for the accumulation of leukocytes at the site of inflamed tissue. The challenge for future investigations will need to be carefully examined: the relations between leukocyte and endothelial cell interactions, the mechanisms of activation of leukocytes and endothelial cells, and the components of the signaling pathways. Information related to these topics will allow a better understanding of the role of leukocytes in inflammatory tissue injury and the development of novel therapeutic strategies.