LIPOPOLYSACCHARIDE INDUCES THE RAPID TYROSINE PHOSPHORYLATION OF THE MITOGEN-ACTIVATED PROTEIN-KINASES ERK-1 AND P38 IN CULTURED HUMAN VASCULAR ENDOTHELIAL-CELLS REQUIRING THE PRESENCE OF SOLUBLE CD14
Rr. Schumann et al., LIPOPOLYSACCHARIDE INDUCES THE RAPID TYROSINE PHOSPHORYLATION OF THE MITOGEN-ACTIVATED PROTEIN-KINASES ERK-1 AND P38 IN CULTURED HUMAN VASCULAR ENDOTHELIAL-CELLS REQUIRING THE PRESENCE OF SOLUBLE CD14, Blood, 87(7), 1996, pp. 2805-2814
Human vascular endothelial cells (HUVECs), which do not display the li
popolysaccharide (LPS) receptor CD14, were examined for protein tyrosi
ne phosphorylation after LPS stimulation in the presence and absence o
f soluble CD14 (sCD14). By phosphotyrosine Western blotting and immuno
-complex kinase assays we show that LPS was capable of inducing in the
se cells rapid protein tyrosine phosphorylation and kinase activation
of two members of the mitogen-activated protein kinase (MAPK) family e
rk-1 and the newly discovered p38, requiring the presence of sCD14. LP
S-induced tyrosine phosphorylation of MAPK was associated with increas
ed transcript- and surface protein expression of intracellular adhesio
n molecule-1 by HUVECs. MAPK phosphorylation and activation was induce
d by LPS in concentrations as little as 30 ng/mL and as early as 15 mi
nutes after stimulation. Furthermore, tyrosine kinase inhibitors such
as Genistein partially inhibited this effect. These results show that
LPS triggers similar signaling events in both CD14(+) myelo-monocytic
cells and cells lacking the putative LPS-receptor CD14, suggesting the
presence of a common, yet unidentified element in LPS-signaling in bo
th cell types. (C) 1996 by The American Society of Hematology.