Essential role of MD-2 in LPS responsiveness and TLR4 distribution

被引：824

作者：

Nagai, Y

Akashi, S

Nagafuku, M

Ogata, M

Iwakura, Y

Akira, S

Kitamura, T

Kosugi, A

Kimoto, M

Miyake, K

机构：

[1] Univ Tokyo, Inst Med Sci, Div Infect Genet, Tokyo, Japan

[2] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Tokyo, Japan

[3] Univ Tokyo, Inst Med Sci, Div Cellular Therapy, Tokyo, Japan

[4] Japan Sci & Technol Corp, CREST, Tokyo, Japan

[5] Saga Med Sch, Dept Immunol, Saga, Japan

[6] Osaka Univ, Sch Med, Sch Allied Hlth Sci, Fac Med, Osaka, Japan

[7] Osaka Univ, Sch Med, Dept Oncogenesis, Osaka, Japan

[8] Osaka Univ, Microbial Dis Res Inst, Osaka, Japan

来源：

NATURE IMMUNOLOGY | 2002年 / 3卷 / 07期

关键词：

D O I：

10.1038/ni809

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Toll-like receptor 4 (TLR4) mediates lipopolysaccharide (LPS) signaling in a variety of cell types. MD2 is associated with the extracellular domain of TLR4 and augments TLR4-dependent LPS responses in vitro. We show here that MD-2(-/-) mice do not respond to LPS, do survive endotoxic shock but are susceptible to Salmonella typhimurium infection. We found that in MD-2(-/-) embryonic fibroblasts, TLR4 was not able to reach the plasma membrane and predominantly resided in the Golgi apparatus, whereas TLR4 was distributed at the leading edge surface of cells in wild-type embryonic fibroblasts. Thus, MD-2 is essential for correct intracellular distribution and LPS-recognition of TLR4.

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页码：667 / 672

页数：6

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