A critical role for monocytes and XXXX in endotoxin-induced endothelial cell activation.

@entity1 @entity32 @entity295 @entity5750 @entity5 @entity39 @entity7965 @entity1192 @entity5751 @entity4495 @entity688
Vascular endothelium activated by endotoxin (lipopolysaccharide [LPS]) and cytokines plays an important role in organ @entity32 and blood leukocyte recruitment observed during @entity295 . Endothelial cells can be activated by LPS directly, after its interaction with LPS-binding protein and soluble @entity5750 in plasma. LPS-LPS-binding protein complexes in blood also interact with monocytes and neutrophils bearing @entity4495 (GPI) anchored membrane @entity5750 ( @entity5751 ), promoting the release of cytokines such as @entity5 @entity39 factor and @entity1192 ). These molecules, in turn, have the capacity to activate endothelial cells providing an indirect pathway for LPS-dependent endothelial cell activation. In this work, we address the relative importance of the direct and the indirect pathway of in vitro LPS-induced @entity1 umbilical vein endothelial cell (HUVEC) activation. Substituting whole blood for plasma resulted in a 1,000-fold enhancement of HUVEC sensitivity to LPS. Both blood- and plasma-dependent enhanced activation of HUVEC were blocked with an anti- @entity5750 monoclonal antibody. Blood from @entity1 with @entity7965 , whose cells lack @entity5751 and other GPI anchored proteins, was unable to enhance LPS activation of HUVEC above the level observed with plasma alone. @entity688 , an inhibitor of monocyte release of cytokines, decreased the blood-dependent enhancement of HUVEC activation by LPS. Blood adapted to small doses of LPS was also less efficient than nonadapted blood in producing this enhancement. Addition of purified mononuclear cells to HUVEC or the transfer of plasma from whole blood incubated with LPS to HUVEC, duplicated the enhancement effect observed when whole blood was incubated with HUVEC. Taken together, these data suggest that the indirect pathway of LPS activation of endothelial cell is mediated by monocytes and @entity5751 through the secretion of a soluble mediator(s). The indirect pathway is far more efficient than the direct, plasma-dependent pathway.
