The Function and Potential Therapeutic Value of Lipopolysaccharide Binding Protein During Gram-Negative Sepsis: Recombinant Expression and Promoter Studies
1994
Endotoxin is a complex molecule found in almost all gram-negative bacteria in the outer cell wall. Once bacteria have invaded, toxic effects towards the host are transmitted by exotoxins that are secreted, or by endotoxin (lipopolysaccharide, LPS), which can act directly or by release from bacteria either after lysis or antibiotic treatment. The chemical structure of LPS was elucidated recently and an important component of LPS, namely lipid A, a part of the molecule that carries all the “endotoxic” capacity, was found [1]. LPS was found to consist of three substructures: (1) the polysaccharides that form the O-specific chain, which has great variability among different bacterial strains; (2) the two-part core, which is more constant throughout the strains; and (3) the lipid A component which is attached to the core, is very constant within different strains, and appears to be the active center of the molecule [2]. Many investigators have studied the events triggered in the host by the appearance of endotoxin. It became clear that LPS is able to induce a stimulation cascade in immune cells, mediated by different soluble factors. Binding proteins and receptors for LPS were postulated and discovered that recognize endotoxin, bind it and subsequently regulate the cellular secretory response induced by LPS. LPS that enters the bloodstream will be bound unspecifically by serum lipoproteins, mainly of the high density class (HDL), which inhibit its effects [3]. Apolipoproteins also have been shown to bind LPS and inhibit its endotoxic potential [4] and low density class lipoproteins (LDL) can bind endotoxin and transport it through endothelial cell layers [5]. Specific binding of LPS in serum occurs by a protein which is called lipopolysaccharide binding protein (LBP) [6–10]. Complexes of LBP and LPS initiate cellular secretory responses that are much stronger than LPS alone. The data obtained so far can be summarized in that LBP enhances LPS-mediated effects on responsive cells without having activation potential of its own.
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