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© The Rockefeller University Press, 0022-1007/1999/6/1777/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 11, June 7, 1999 1777-1782

Articles

MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4

Rintaro Shimazu, Sachiko Akashi, Hirotaka Ogata, Yoshinori Nagai, Kenji Fukudome, Kensuke Miyake, and Masao Kimoto

From the Department of Immunology, Saga Medical School, Saga, Japan

Toll-like receptor 4 (TLR4) is a mammalian homologue of Drosophila Toll, a leucine-rich repeat molecule that can trigger innate responses against pathogens. The TLR4 gene has recently been shown to be mutated in C3H/HeJ and C57BL/10ScCr mice, both of which are low responders to lipopolysaccharide (LPS). TLR4 may be a long-sought receptor for LPS. However, transfection of TLR4 does not confer LPS responsiveness on a recipient cell line, suggesting a requirement for an additional molecule. Here, we report that a novel molecule, MD-2, is requisite for LPS signaling of TLR4. MD-2 is physically associated with TLR4 on the cell surface and confers responsiveness to LPS. MD-2 is thus a link between TLR4 and LPS signaling. Identification of this new receptor complex has potential implications for understanding host defense, as well as pathophysiologic, mechanisms.

Key Words: leucine-rich repeat • RP105 • MD-1 • nuclear factor {kappa}B • signaling

Address correspondence to Kensuke Miyake, Department of Immunology, Saga Medical School, Nabeshima, Saga 849-8501, Japan. Phone: 81-952-34-2256; Fax: 81-952-34-2049; E-mail: miyake{at}post.saga-med.ac.jp

R. Shimazu and S. Akashi contributed equally to this study.

Abbreviations used: GAPDH, glyceraldehyde-3-phosphate dehydrogenase; LRR, leucine-rich repeat; NF, nuclear factor; RT, reverse transcriptase; TLR, Toll-like receptor.


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