Evidence for E-selectin complement regulatory domain mRNA splice variants in the rat.

The adhesion protein E-selectin is one mediator of endothelial cell-leukocyte interaction during acute inflammation. To investigate the molecular regulation of E-selectin function, we have examined the expression of E-selectin mRNA in target rat tissues after administration of lipopolysaccharide, a potent inducer of acute inflammation. In the course of these studies we isolated two unique rat E-selectin cDNA fragments. Both cDNA fragments show extensive nucleotide sequence homology to previously isolated mouse and human E-selectin cDNAs. However, they differ for the presence of sequences that encode complement regulatory domain-5 (CR5). Previous studies have shown that different animal species express E-selectin mRNAs that encode different numbers of CR domains. The isolation of these two rat E-selectin cDNA fragments, which differ only for the presence of CR5, represents the first direct evidence for the existence of E-selectin CR-variant mRNAs in the same species. Moreover, the sequence of the CR5(-) cDNA is consistent with its origin from an mRNA splice variant of a CR5(+) mRNA. We have demonstrated the presence of the two predicted mRNA species in rat heart tissue and have investigated their expression in response to lipopolysaccharide. Although both mRNA variants were greatly induced by lipopolysaccharide, the CR5(-) form was more abundant in both treated and control tissues. This difference in mRNA abundance may indicate different levels of CR5 variant proteins that perform functionally distinct tasks in E-selectin dependent inflammatory processes.