RO-heparin Inhibits L-Selectin-mediated Neutrophils Adhesion to Vascular Endothelium Under Flow Conditions

Abstract

Selectins are carbohydrate-binding cell adhesion molecules that play a major role in the initiation of inflammatory responses. Accumulaed evidence has suggested that heparin's anti-inflammatory effects are mainly mediated by blocking L- or P-selectin-initiated cell adhesion. Recently, we have reported that periodate-oxidized, borohydride-reduced heparin (RO-heparin) can inhibit P-selectin-mediated acute inflammation. Here we further examined the effect of RO-heparin on the adhesion of L-selectin-mediated leukocytes to vascular endothelium under flow conditions in vivo and in vitro. The results show that RO-heparin with a low anticoagulant activity can effectively reduce leucocyte rolling on thioglycollate-induced rat mesenteric venules and L-selectin-metadiated neutrophil rolling on TNF-α-induced human umbilical vein endothelial cells (HUVECs) under flow conditions. Our findings suggest that the effect of RO-heparin on inflammatory responses is mainly a result of its inhibiting the interaction between P- or L-selectin and its ligands. The findings also suggest that RO-heparin may be useful in preventing inflammation diseases.