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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.
Youn, Ju Ho; Oh, Young Joo; Kim, Eun Sook; Choi, Ji Eun; Shin, Jeon-Soo.
Afiliação
  • Youn JH; Department of Microbiology, Brain Korea 21 Project for Medical Science, National Core Research Center for Nanomedical Technology, Yonsei University College of Medicine, Seoul, Republic of Korea.
J Immunol ; 180(7): 5067-74, 2008 Apr 01.
Article em En | MEDLINE | ID: mdl-18354232
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.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Monócitos / Lipopolissacarídeos / Fator de Necrose Tumoral alfa / Receptores de Lipopolissacarídeos / Proteína HMGB1 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: J Immunol Ano de publicação: 2008 Tipo de documento: Article
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Monócitos / Lipopolissacarídeos / Fator de Necrose Tumoral alfa / Receptores de Lipopolissacarídeos / Proteína HMGB1 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: J Immunol Ano de publicação: 2008 Tipo de documento: Article