Cell adhesion molecules, leukocyte trafficking, and strategies to reduce leukocyte infiltration.
Leukocyte-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 beta2 integrins after leukocyte exposure to cytokines and pro-inflammatory mediators, (2) adherence of leukocyte beta2 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 beta1 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 beta2 integrins, 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.
Radi
Z A
ZA
Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames 50011-1250, USA.
Kehrli
M E
ME
Ackermann
M R
MR
D000820:Animal Diseases / Q000276:immunology / Q000503:physiopathology; D000818:Animals; D015815:Cell Adhesion Molecules / Q000494:pharmacology*; D002450:Cell Communication; D007136:Immunoglobulins / Q000276:immunology / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D016023:Integrins / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000494:pharmacology; D007962:Leukocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D019087:Selectins / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D016023:Integrins; D019087:Selectins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1