HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Divergent Inducible Expression of P-Selectin and E-Selectin in Mice and Primates

We used in vitro and in vivo approaches to examine whether tumor necrosis factor-a (TNF-a) and oncostatin M (OSM), cytokines that bind to distinct classes of receptors, differentially regulate expression of Pand E-selectin in murine and primate endothelial cells. In human umbilical vein endothelial cells, TNF-a rapidly increased mRNA for E-selectin but not P-selectin. OSM elicited little or no change in mRNA for E-selectin, but induced a delayed and prolonged increase in P-selectin mRNA. TNF-a and OSM did not cooperate to further enhance Por E-selectin mRNA. Intravenous infusion of Escherichia coli, which markedly elevates plasma lipopolysaccharide and TNF-a, increased mRNA for E-selectin but not P-selectin in baboons. In murine bEnd.3 endothelioma cells, TNF-a and OSM individually and cooperatively increased mRNA and protein for both Pand E-selectin. Intravenous injection of these cytokines also individually and cooperatively increased mRNA for Pand E-selectin in mice. We conclude that the murine Pand E-selectin genes respond to both TNF-a and OSM, whereas the primate Pand E-selectin genes have much more specialized responses. Such differences should be considered when extrapolating the functions of Pand E-selectin in murine models of inflammation to humans. r 1999 by The American Society of Hematology.