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

Autor: Kenji Fukudome, Kensuke Miyake, Masao Kimoto, Hirotaka Ogata, Yoshinori Nagai, Rintaro Shimazu, Sachiko Akashi
Rok vydání: 1999
Předmět:
Zdroj: The Journal of Experimental Medicine
ISSN: 1540-9538
0022-1007
DOI: 10.1084/jem.189.11.1777
Popis: 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.
Databáze: OpenAIRE