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High mobility group box 1 protein binding to lipopolysaccharide facilitates transfer of lipopolysaccharide to CD14 and enhances lipopolysaccharide-mediated TNF-alpha production in human monocytes.

Authors
 Ju Ho Youn  ;  Young Joo Oh  ;  Eun Sook Kim  ;  Ji Eun Choi  ;  Jeon-Soo Shin 
Citation
 JOURNAL OF IMMUNOLOGY, Vol.180(7) : 5067-5074, 2008 
Journal Title
JOURNAL OF IMMUNOLOGY
ISSN
 0022-1767 
Issue Date
2008
MeSH
Animals ; CHO Cells ; Catalysis ; Cricetinae ; Cricetulus ; HMGB1 Protein/genetics ; HMGB1 Protein/metabolism* ; Humans ; Leukocytes/drug effects ; Leukocytes/metabolism ; Lipopolysaccharide Receptors/metabolism* ; Lipopolysaccharides/pharmacology* ; Micelles ; Monocytes/drug effects* ; Monocytes/metabolism* ; Protein Binding ; Solubility ; Surface Plasmon Resonance ; Tumor Necrosis Factor-alpha/biosynthesis*
Keywords
Animals ; CHO Cells ; Catalysis ; Cricetinae ; Cricetulus ; HMGB1 Protein/genetics ; HMGB1 Protein/metabolism* ; Humans ; Leukocytes/drug effects ; Leukocytes/metabolism ; Lipopolysaccharide Receptors/metabolism* ; Lipopolysaccharides/pharmacology* ; Micelles ; Monocytes/drug effects* ; Monocytes/metabolism* ; Protein Binding ; Solubility ; Surface Plasmon Resonance ; Tumor Necrosis Factor-alpha/biosynthesis*
Abstract
LPS-binding protein (LBP) is a central mediator that transfers LPS to CD14 to initiate TLR4-mediated proinflammatory response. However, a possibility of another LPS transfer molecule has been suggested because LBP-deficient mice showed almost normal inflammatory response after LPS injection. In this study, we describe the novel finding that high mobility group box 1 protein (HMGB1) recently identified as a mediator of sepsis has a function of LPS transfer for a proinflammatory response. We used ELISA and surface plasmon resonance to show that HMGB1 binds LPS in a concentration-dependent manner and that the binding is stronger to lipid A moiety than to the polysaccharide moiety of LPS. This binding was inhibited by LBP and polymyxin B. Using native PAGE and fluorescence-based LPS transfer analyses, we show that HMGB1 can catalytically disaggregate and transfer LPS to both soluble CD14 protein and to human PBMCs in a dose-dependent manner. However, this effect was dramatically reduced to the baseline level when HMGB1 was heat inactivated. Furthermore, a mixture of HMGB1 and LPS treatment results in a higher increase in TNF-alpha production in human PBMCs and peripheral blood monocytes than LPS or HMGB1 treatment alone or their summation. Thus, we propose that HMGB1 plays an important role in Gram-negative sepsis by catalyzing movement of LPS monomers from LPS aggregates to CD14 to initiate a TLR4-mediated proinflammatory response
Files in This Item:
T200800497.pdf Download
DOI
18354232
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eun Sook(김은숙)
Shin, Jeon Soo(신전수) ORCID logo https://orcid.org/0000-0002-8294-3234
Youn, Ju Ho(윤주호)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/106680
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