Molecular mechanisms of leukocyte recruitment in the inflammatory process

The microcirculation constitutes the functional interface between the circulating blood and the interstitial space. To gain access to sites of inflammation, leukocytes must pass the endothelial barrier. The recruitment paradigm encompasses leukocyte margination, capture, rolling, activation, firm adhesion, and transmigration. Recent experimental work has shown that E-, L- and P-selectins and alpha 4 integrins can mediate leukocyte rolling. Upon activation by chemokines, complement peptides or lipid mediators, firm adhesion is afforded by beta 1 and beta 2 integrins, InterCellular Adhesion Molecules (ICAMs) and Vascular Cell Adhesion Molecule-1 (VCAM-1). Beta 1 and beta 2 integrins as well as Platelet-Endothelial Cell Adhesion Molecule-1 (PECAM-1) have been shown to be involved in transmigration. Intravital microscopic techniques have been instrumental in applying the conceptual advances of cell and molecular biology to the in vivo situation. This review focuses on the current understanding of the leukocyte recruitment paradigm as suggested by in vivo observations and in vitro model systems. The paradigm of neutrophil recruitment is presented to serve as a model for the recruitment mechanisms of other inflammatory cells.