Limited endothelial E- and P-selectin expression in MRL/lpr lupus-prone mice.

Abstract

Inflammation in MRL/lpr mice may involve dysfunctional leucocyte-endothelial cell (EC) interactions. Previously, we have shown that intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) increase with age in a tumour necrosis factor alpha (TNF alpha)- and interleukin-1 (IL-1)-dependent manner. The object of this study was to determine the expression of E- and P-selectin. Selectin expression was quantified in MRL/lpr mice and BALB/c controls by intravenous injection of differentially radio-labelled antibodies. E-selectin, but not P-selectin, was up-regulated in the kidneys of older mice. Neither was up-regulated elsewhere. There was no defect in selectin inducibility, as a further inflammatory stimulus (intraperitoneal lipopolysaccharide) resulted in up-regulation. Serum from older MRL/lpr did not induce selectin expression by EC in vitro. The increase in E-selectin in the kidney may contribute to the development of glomerulonephritis. However, the lack of systemic E- and P-selectin expression may represent a protective mechanism which limits the interaction between leucocytes and the endothelium in the chronic inflammatory context.