Cell adhesion molecules, leukocyte trafficking, and strategies to reduce leukocyte infiltration

Leukocyte-endothelial cell interactions are mediated by various cell adhesi on molecules. These interactions are important for leukocyte extravasation and trafficking in all domestic animal species. An initial slowing of leuko cytes on the vascular endothelium is mediated by selectins. This event is f ollowed by (1) activation of beta (2) integrins after leukocyte exposure to cytokines and proinflammatory mediators, (2) adherence of leukocyte beta ( 2) integrins to vascular endothelial ligands (eg, intercellular adhesion mo lecule-1 [ICAM-1]), (3) extravasation of leukocytes into tissues through ti ght junctions of endothelial cells mediated by platelet and endothelial cel l adhesion molecule-1 (PECAM-1), and (4) perivascular migration through the extracellular matrix via beta (1) integrins. Inhibiting excessive leukocyt e egress and subsequent free radical-mediated damage caused by leukocyte co mponents may attenuate or eliminate tissue damage. Several methods have bee n used to modify leukocyte, infiltration in various animal models. These me thods include nonspecific inhibition of pro-inflammatory mediators and adhe sion molecules by nonsteroidal anti-inflammatory drugs (NSAIDs) and glucoco rticoids, inhibition of cytokines and cytokine receptors, and inhibition of specific types of cell adhesion molecules, with inhibitors such as peptide s and antibodies to beta (2) integrins, and inhibitors of selectins, ICAMs, and vascular cell adhesion molecule-1 (VCAM-1). By understanding the cellu lar and molecular events in leukocyte-endothelial cell interactions, therap eutic strategies are being developed in several animal models and diseases in domestic animal species. Such therapies may have clinical benefit in the future to overcome tissue damage induced by excessive leukocyte infiltrati on.