LIPOPOLYSACCHARIDE-BINDING PROTEIN PARTICIPATION IN CELLULAR ACTIVATION BY LPS

Lipopolysaccharide binding protein (LBP) is a plasma protein that play s an important intermediary role in host-endotoxin (LPS) interactions. LBP binds with high affinity to the lipid A portion of LPS and then i nteracts with the monocytic differentiation antigen CD14 to markedly u p-regulate TNF-alpha production by mononuclear phagocytes. In the pres ence of LBP, 100-fold less LPS is required to trigger this cytokine re sponse. LBP has been implicated in the interaction of LPS with both CD 14(+) (monocytes, macrophages, neutrophils) and CD14-cells (endothelia l and epithelial cells) to promote such varying responses as secretion of cytokines and nitric oxide (NO), expression of adhesion molecules, production of tissue factor, and activation of neutrophils. Non-CD 14 -bearing cells, such as endothelial cells, can also respond to LPS thr ough this pathway via the soluble form of CD14, an interaction that is similarly enhanced by LBP. Recently, it has been proposed that LBP ca nnot only potentiate host responses to LPS but can also facilitate the neutralization of LPS under certain conditions. LBP has been describe d as acting as a lipoprotein transfer protein facilitating the transfe r of LPS both to the target receptor (CD14) and lipoprotein (HDL).