Cell Adhesion Molecules, Leukocyte Trafficking, and Strategies to Reduce Leukocyte InfiltrationJournal of Veterinary Internal Medicine
AbstractLeukocyte-endothelial cell interactions are mediated by various cell adhesion molecules. These interactions are important for leukocyte extravasation and trafficking in all domestic animal species. An initial slowing of leukocytes on the vascular endothelium is mediated by selectins. This event is followed by (1) activation of β2 integrins after leukocyte exposure to cytokines and proinflammatory mediators, (2) adherence of leukocyte β2 integrins to vascular endothelial ligands (eg, intercellular adhesion molecule-1 [ICAM-1]), (3) extravasation of leukocytes into tissues through tight junctions of endothelial cells mediated by platelet and endothelial cell adhesion molecule-1 (PECAM-1), and (4) perivascular migration through the extracellular matrix via β1 integrins. Inhibiting excessive leukocyte egress and subsequent free radical-mediated damage caused by leukocyte components may attenuate or eliminate tissue damage. Several methods have been used to modify leukocyte infiltration in various animal models. These methods include nonspecific inhibition of pro-inflammatory mediators and adhesion molecules by nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, inhibition of cytokines and cytokine receptors, and inhibition of specific types of cell adhesion molecules, with inhibitors such as peptides and antibodies to β2integrins, and inhibitors of selectins, ICAMs, and vascular cell adhesion molecule-1 (VCAM-1). By understanding the cellular and molecular events in leukocyte-endothelial cell interactions, therapeutic 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 infiltration.
RightsWorks produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.
Date AvailableFebruary 26, 2013
Citation InformationZaher A. Radi, Marcus E. Kehrli and Mark R. Ackermann. "Cell Adhesion Molecules, Leukocyte Trafficking, and Strategies to Reduce Leukocyte Infiltration" Journal of Veterinary Internal Medicine Vol. 15 Iss. 6 (2001) p. 516 - 529
Available at: http://works.bepress.com/mark_ackermann/47/