Relative roles of leukocyte and endothelial cell activation in affecting their adhesion: the role of the glycocalyx

摘要

The inflammatory process consists of a sequence of events that hinges upon the mechanics of adhesion between leukocytes (WBCs) and endothelial cells (ECs). The selectin mediated rolling of leukocytes, followed by integrin governed firm adhesion of WBCs to the endothelium represent pivotal processes that precede the diapedesis of WBCs through interendothelial clefts. Initiation of the sequence of WBC rolling, adhesion and diapedesis has been shown to be dependent upon the release of cytokines and/or various peptides from parenchymal tissue which activate either the WBC or EC. Considerable evidence suggests that WBC activation is the principal event leading to firm adhesion, manifest by either externalization of membrane bound integrins (CD 11/18) from submembrane vesicles or conformational changes of exposed integrins on the WBC surface. The binding of these WBC-bound molecules to ligands on the EC surface, principally ICAM-l, thus leads to the firm adhesion of leukocytes. Numerous studies have demonstrated that when the adhesion process is initiated by, for example, the topical application of formyl peptides to an exposed tissue, WBCs rapidly accumulate along the walls of post-capillary venules. This adhesion may have a profound effect on the hemodynamics of blood flow in the microvasculature. As few as 12 WBCs adhering to the EC per 100 um of venule length has been shown to obstruct the microvessel lumen to induce a two-fold rise in the hemodynamic resistance to flow.