The Role of Lipopolysaccharide Binding Protein in the LPS Activation and Phagocytotic Response of Kupffer Cells
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Though common only since the 1950s, Gram-negative bacterial sepsis leads to thousands of deaths every year. No successful treatments or preventive measures currently exist. Lipopolysaccharide (LPS), a constituent of Gram-negative bacteria, stimulates host macrophages by inducing a phagocytotic response in which the macrophages engulf the bacteria. In addition, the macrophages are caused to release large quantities of tumor necrosis factor (TNF) and other cytokines. These factors can trigger inflammatory reactions in the host body that lead to tissue damage and lethal shock. Lipopolysaccharide binding protein (LBP) complexes with LPS to facilitate this macrophage response. An especially influential group of cells that playa role in the systemic reaction to LPS are Kupffer cells that reside in the liver. They are a unique group of macrophages that provide a major site for LPS response and clearance, yet relatively little is known about them. Since Kupffer cell over-activation contributes significantly to the pathological process in sepsis, learning more about this molecular mechanism will allow new areas of treatment to be explored. This study investigated the ways by which LBP can alter Kupffer cell phagocytosis and activation. By stimulating Kupffer cells with varying doses of LPS and LBP, it was concluded that LBP does not affect the phagocytotic response. However, low concentrations of LBP were found to augment TNF production, while higher concentrations were not found to have this effect. These results indicate the likelihood that a rise in LBP levels exerts a protective effect on the liver during injurious states.