Expression of VCAM-1 and E-selectin in an in vivo model of endothelial activation

Abstract

Vascular cell adhesion molecule 1 (VCAM-1) and E-selectin (or endothelial-leukocyte adhesion molecule 1) are inducible endothelial cell adhesion molecules that play a role in the recruitment of leukocytes into sites of inflammation. Information about the spatial and temporal pattern of induced expression of these leukocyte adhesion molecules in vivo is limited. This study reports the expression profile of VCAM-1 and E-selectin in various mouse tissues after lipopolysaccharide administration. Using rat complementary DNA probes for VCAM-1 and E-selectin, Northern blot analysis showed a marked increase in transcript levels for both adhesion molecules in lung, heart, and kidney. Maximal transcript levels for both VCAM-1 and E-selectin were observed at 3-6 hours and declined to low, constitutive levels of expression at 48 hours. Consistent with the Northern blot results, immunoperoxidase analysis revealed focal endothelial cell expression of VCAM-1 in control animals. Following lipopolysaccharide administration, VCAM-1 expression increased dramatically in all vascular beds examined, although the response was heterogeneous. Widespread induced expression of VCAM-1 on cells other than vascular endothelium was not seen. Neither basal nor induced expression correlated with leukocyte adhesion. Signals other than the expression of endothelial leukocyte adhesion molecules are required in vivo for leukocyte infiltration in this murine model of systemic endothelial activation.