The microcirculation and inflammation: modulation of leukocyte-endothelial cell adhesion

Abstract

The accumulation of leukocytes in inflamed tissue results from adhesive interactions between leukocytes and endothelial cells within the microcirculation. These adhesive interactions and the excessive filtration of fluid and protein that accompanies an inflammatory response are largely confined to one region of the microvasculature: postcapillary venules. The nature and magnitude of the leukocyte-endothelial cell adhesive interactions that take place within postcapillary venules are determined by a variety of factors, including expression of adhesion molecules on leukocytes and/or endothelial cells, products of leukocyte (superoxide) and endothelial cell (nitric oxide) activation, and the physical forces generated by the movement of blood along the vessel wall. The contribution of different adhesion molecules to leukocyte rolling, adherence, and emigration in venules is discussed. Emerging views on potential endogenous antiadhesion molecules produced by endothelial cells as well as the influence of alterations in shear rate on leukocyte adhesion are addressed. Finally, the pathophysiological significance of the microvascular responses to inflammation are discussed in terms of adhesion-directed strategies for the treatment of different cardiovascular diseases and circulatory disorders.

Increased P-selectin gene expression in the liver vasculature and its role in the pathophysiology of neutrophil-induced liver injury in murine endotoxin shock

“…P-selectin is critical for the initial neutrophil margination (rolling phenomenon) in a variety of postcapillary venules [7,10,15]. This rolling process is a prerequisite for firm adherence in these vessels and the subsequent transendothelial migration of neutrophils [12,13].…”

“…Neutrophil recruitment to inflammatory sites requires the coordinated action of various adhesion molecules on the leukocyte as well as on the vascular endothelium [7]. It is generally accepted that the initial contact of neutrophils with endothelial cells occurs through selectins and their ligands [8][9][10][11][12].…”

Glutathione Peroxidase-Deficient Mice Are More Susceptible to Neutrophil–Mediated Hepatic Parenchymal Cell Injury During Endotoxemia: Importance of An Intracellular Oxidant Stress

“…Because of the potential detrimental effects of neutrophils in many clinical situations, various aspects of the basic mechanisms of neutrophil accumulation at an inflammatory site and the molecular mechanisms of injury have been subject to extensive investigation during the last decade. 4,5 The goal is to identify targets for potential therapeutic interventions that reduce the inflammatory response without affecting vital host defense mechanisms.…”

NSAIDs upregulate β2‐integrin expression on human neutrophils through a calcium‐dependent pathway

“…6,7 The P-selectin, E-selectin and intercellular adhesion molecule 1 (ICAM-1), expressed on the endothelial cells lining the blood vessels, interact with counter-receptors L-selectin, Mac-1 (CD11b/CD18), LFA-1 and (Cd11a/ CD18), etc., on neutrophils, allowing PMN to slow down via a rolling motion on endothelial cells, stop and transmigrate into surrounding tissues. 6,7 However, the mechanisms by which different NSAIDs promote adhesive events into the gastric microcirculation remain unclear. A recent in vitro study on human PMN and umbilical vein endothelial cells (HUVEC) suggests a direct pro-adhesive effect.…”