Leukocytes migrate across resting endothelium if an exogenous chemoattractant is present (Huang et al 1992; Furie et al 1989; Furie et al 1991). For example, addition of a gradient of IL-8 or fMLP results in transmigration, which is dose dependent and can cause 50-90% of the neutrophils to transmigrate (Furie et al 1991; Smith et al 1991; Smith et al 1994). This has been termed "leukocyte driven" or chemotactic transmigration. The pathophysiological hallmark of established inflammatory transmigration is endothelial activation, an event requiring transcription and protein synthesis. As a result adhesion molecules are upregulated, inflammatory mediators are produced, and the endothelium secretes chemoattractants, all of which contribute to transmigration. Endothelial are critical for transmigration. They are secreted in significant amounts: concentrations in vitro reach those producing maximal chemotactic responses (Smith, 1994). The stimulus for endothelial activation in vivo is probably local production of cytokines and other inflammatory mediators released on tissue injury.

A number of adhesion molecules have been implicated in transmigration, although the level of confidence in their actual involvement varies. Here, we will discuss the roles of PECAM-1, ICAM-1, VE-cadherin, CD11a/CD18 (LFA-1), IAP (CD47) and VLA-4 (41 integrin).

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