Lipopolysaccharide Binding Protein Participation in Cellular Activation by LPS

Abstract

Lipopolysaccharide binding protein (LBP) is a plasma protein that plays an important intermediary role in host-endotoxin (LPS) interactions. LBP binds with high affinity to the lipid A portion of LPS and then interacts with the monocytic differentiation antigen CD 14 to markedly up-regulate TNF-α production by mononuclear phagocytes. In the presence of LBP, 100-fold less LPS is required to trigger this cytokine response. LBP has been implicated in the interaction of LPS with both CD14+ (monocytes, macrophages, neutrophils) and CD14-cells (endothelial 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 through this pathway via the soluble form of CD14, an interaction that is similarly enhanced by LBP. Recently, it has been proposed that LBP cannot only potentiate host responses to LPS but can also facilitate the neutralization of LPS under certain conditions. LBP has been described as acting as a lipoprotein transfer protein facilitating the transfer of LPS both to the target receptor (CD 14) and lipoprotein (HDL).