114 - Molecular Mechanisms of Leukocyte Transendothelial Cell Migration

Summary

In this chapter, the focus is on three areas of interest relevant to the study of leukocyte transmigration as an output device of the vascular endothelium. The mechanisms underlying leukocyte adhesion and recruitment have been discussed in earlier chapters, and readers are referred there to obtain this information. The first section presents a brief historical perspective on the history of inflammation and, in particular, leukocyte transmigration. Second, the signaling capacity of endothelial adhesion molecules that capture leukocytes and mediate adhesion and transmigration is discussed. It is apparent that these adhesion “receptors,” in particular intercellular adhesion molecule (ICAM)-1, signal during their engagement with leukocytes. Third, the process of leukocyte diapedesis at endothelial cell (EC)–cell lateral junctions and the transient and reversible alterations that occur in junctional components (e.g., transient loss of vascular endothelial [VE]-cadherin) during transmigration is addressed. This area is clearly of interest, because prolonged and/or excessive leukocyte recruitment and the inflammatory milieu together are predicted to have negative affects on the permeability barrier function of the endothelium. Finally, a discussion is included on a somewhat controversial aspect of diapedesis, namely, do leukocytes undergo diapedesis at junctional or nonjunctional sites, and what factors dictate the location? Each of these topics can be envisioned as altering or modulating the output of the endothelium.

HISTORICAL PERSPECTIVE

The study of inflammation began more that two thousand years ago with the Egyptians (see the excellent review chapter by Klaus Ley; Ref. 1). This culture described some of the signs and consequences of inflammation, notably descriptions of abscess and ulcer.