부산대학교 도서관

LPS-binding protein (LBP) recognizes bacterial LPS and transfers it to CD14, thereby enhancing host cell stimulation and eventually resulting in pathogenic states such as septic shock. The study of agents with the capacity to block this interaction (LBPderived peptides) offers a new therapeutic strategy for septic disorders. TNF-alpha production during the initial states of the inflammatory response is an important biological marker of tissue damage in animal models of septic shock. We have now evaluated the functional impact of two LBP-derived peptides (LBP86-99 and LBPK95A) in a mouse model of endotoxic shock. The sequence of these peptides corresponds to the LPS binding motif of human LBP and a single point mutant, respectively. We determined serum levels of TNF-alpha (by ELISA) and TNF-alpha mRNA expression in liver tissue (by RT-PCR) in mice receiving a lethal dose of Serratia marcescens LPS and the peptides (50 µg/mouse). We found a significative reduction of TNF-alpha levels with peptides treatment associated with survival improvements. These results were confirmed in liver tissue using western blotting, which demonstrates the decrease of this proinflamatory cytokine in this organ. We conclude that these LBP-derivated peptides have a protective effect in this animal model which is closely related with their ability to reduced TNF-alpha synthesis. Despite the limitations of any murine sepsis model, the results indicate that LBP-derived peptides could have beneficial effects during gram-negative sepsis. [ABSTRACT FROM AUTHOR]