Recombinant human bactericidal/permeability-increasing protein (rBPI23) is a universal lipopolysaccharide-binding ligand.
AUTOR(ES)
Appelmelk, B J
RESUMO
A recombinant 23-kDa protein (rBPI23) derived from human bactericidal/permeability-increasing protein (BPI) possesses potent endotoxin-neutralizing abilities in vitro and in vivo. Binding of rBPI23 to those endotoxins (lipopolysaccharides [LPSs]) encountered clinically would be a prerequisite for efficacy in decreasing mortality among patients suffering from gram-negative sepsis and shock, a disease state in which an etiological role for LPS has been implicated. rBPI23 binds well to lipid A (n = 7), to rough-mutant O-chain-deficient LPS (n = 18, Re to Ra chemotypes), to lipid A-core covalently linked to the O chain, to LPSs from clinically relevant serotypes (n = 100), and to bacterial cells (n = 88) of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, the species most often implicated in clinical gram-negative sepsis and shock. Significant binding of rBPI23 to these antigens took place at rBPI23 concentrations of 1 to 500 ng/ml (median, 16 to 32 ng/ml). Binding did not involve 3-deoxy-D-manno-octulosonate of the inner core. Determining the exact epitope recognized by rBPI23 would require further studies with synthetic lipid A substructures. The demonstrated ability of rBPI23 to universally bind LPS provides a sound basis for further testing of its endotoxin-neutralizing abilities, including clinical trials.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=302994Documentos Relacionados
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