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J Exp Med. 1999 Jun 7;189(11):1777-82.

MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4.

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  • 1Department of Immunology, Saga Medical School, Saga, Japan.

Abstract

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.

PMID:
10359581
[PubMed - indexed for MEDLINE]
PMCID:
PMC2193086
Free PMC Article

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