HETEROGENEITY OF EXPRESSION OF E-SELECTINS AND P-SELECTINS IN-VIVO

A novel technique involving radiolabeled monoclonal antibodies was use d to characterize and compare the expression of E- and P-selectin on u nstimulated, histamine-challenged, and endotoxin-challenged endothelia l cells in various tissues of the mouse. Under unstimulated conditions , E-selectin was absent in all organs, but significant expression of P -selectin was observed in several organs. Histamine induced a rapid ti me-dependent upregulation of P-selectin, with the largest responses ob served in mesentery and lung. Significant fold elevations in P-selecti n expression occurred as early as 5 minutes after the histamine inject ion and remained elevated up to 1 hour. Histamine-induced P-selectin u pregulation was inhibited by the H-1 receptor antagonist diphenhydrami ne, whereas the H-2 receptor antagonist cimetidine had no effect. Endo toxin (lipopolysaccharide [LPS]) also induced a time-dependent express ion of P-selectin that reached a maximum between 4 and 8 hours after e ndotoxin administration. LPS-induced upregulation of P-selectin was gr eatest in heart and stomach, which exhibited insignificant constitutiv e expression of P-selectin. LPS also induced a time-dependent upregula tion of E-selectin, with maximal expression occurring 3 to 5 hours aft er intraperitoneal administration. The lung and small intestine exhibi ted the largest responses to LPS challenge. Histamine administration d id not affect E-selectin expression in any tissue. E- and P-selectin-d eficient mice were used to test the specificity of monoclonal antibody binding in unstimulated, histamine-challenged, and LPS-stimulated tis sues. Vascular binding of the radiolabeled E-selectin and P-selectin m onoclonal antibodies was not observed in the respective deficient mice . These findings suggest that P-selectin is constitutively expressed o n vascular endothelium in some tissues of the mouse and that there are significant regional differences in the magnitude and time course of histamine- and endotoxin-induced P-selectin expression. In contrast, E -selectin appears to be absent on unstimulated vascular endothelium bu t is upregulated within 3 hours after the administration of endotoxin in most tissues.