Interleukin-1 Stimulation of Vascular Endothelial Cell Adhesiveness for Leucocytes: In Vitro And In Vivo Studies

Abstract

Under normal conditions, circulating leukocytes adhere to the vascular bed through a reversible adhesive interaction with endothelial cells (ECs).1 However, a dramatic increase in leukocyte adherence is observed following tissue injury which is restricted to vessels in the affected area.2 During the early stages neutrophils predominate.1 Although this is a fundamental aspect of inflammation, little is known of the actual mechanisms which initiate leukocyte adhesion. It has been known for some time that divalent cations are essential and removal of cell surface sialic acid residues augments EC-leukocyte adhesion.1,3 Development of EC culture techniques has permitted more extensive studies on the adhesive interactions between these cells. Recent observations suggest a role for altered fibronectin,4 chemotactic factors5,6 and arachidonic acid metabolites,7,8 indicating the polymorphonuclear leukocyte (PMN) as the target cell. Enhanced EC-PMN adhesion following preincubation of ECs with C’5a3, or C’5a desarg.,9 suggested that these cells could be stimulated to become hyperadhesive for PMNs, although these observations are controversial.5 Leukotriene B4 (LtB4) has been shown to initiate adhesion of human PMNs to bovine ECs immediately after contact with endothelium in vitro, although the adhesiveness of PMNs was also directly affected by LtB4.7,10