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-alpha (TNF-alpha) and oncostatin M (OSM), cytokines that bind to distinct classes of receptors, differentially regulate expression of P- and E-selectin in murine and primate endothelial cells. In human umbilical vein endothelial cells, TNF-alpha 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-alpha and OSM did not cooperate to further enhance P- or E-selectin mRNA. Intravenous infusion of Escherichia coli, which markedly elevates plasma lipopolysaccharide and TNF-alpha, increased mRNA for E-selectin but not P-selectin in baboons. In murine bEnd.3 endothelioma cells, TNF-alpha and OSM individually and cooperatively increased mRNA and protein for both P- and E-selectin. Intravenous injection of these cytokines also individually and cooperatively increased mRNA for P- and E-selectin in mice. We conclude that the murine P- and E-selectin genes respond to both TNF-alpha and OSM, whereas the primate P- and E-selectin genes have much more specialized responses. Such differences should be considered when extrapolating the functions of P- and E-selectin in murine models of inflammation to humans.