INTRATRACHEAL ADMINISTRATION OF ENDOTOXIN AND CYTOKINES .8. LPS INDUCES E-SELECTIN EXPRESSION - ANTI-E-SELECTIN AND SOLUBLE E-SELECTIN INHIBIT ACUTE-INFLAMMATION

E-selectin is an inducible endothelial adhesion molecule that binds ne utrophils. E-selectin mRNA is not constitutively detectable in the lun gs of rats. Intratracheal injection of LPS induces pulmonary E-selecti n mRNA expression at 2-4 h. Intratracheal injection of LPS followed at 2 and 4 h by intravenous injection of mouse F(ab')(2) or F(ab') anti- E-selectin monoclonal antibody inhibits the emigration of neutrophils into the bronchoalveolar space at 6 h by 50-70%. TNF and IL-6 bioactiv ity are not decreased in bronchoalveolar lavage fluid after treatment with anti-E-selectin antibody as compared to controls, suggesting that the anti-E-selectin does not affect the magnitude of the LPS-initiate d cytokine cascade. Intratracheal injection of LPS followed at 2 and 4 h by intravenous injection of soluble E-selectin inhibits neutrophili c emigration at 6 h by 64%, suggesting that endogenous soluble E-selec tin shed from activated endothelium may play a role in the endogenous down-regulation of acute inflammation. E-selectin-mediated adhesion of neutrophils to endothelium appears crucial to the full development of the acute inflammation response.