Physical contact between lipopolysaccharide and toll-like receptor 4 revealed by genetic complementation

A. Poltorak, P. Ricciardi-Castagnoli, S. Citterio, B. Beutler

Research output: Contribution to journalArticle

383 Scopus citations

Abstract

Some mammalian species show an ability to discriminate between different lipopolysaccharide (LPS) partial structures (for example, lipid A and its congener LA-14-PP, which lacks secondary acyl chains), whereas others do not. Using a novel genetic complementation system involving the transduction of immortalized macrophages from genetically unresponsive C3H/HeJ mice, we now have shown that the species-dependent discrimination between intact LPS and tetra-acyl LPS partial structures is fully attributable to the species origin of Toll-like receptor 4 (Tlr4), an essential membrane-spanning component of the mammalian LPS sensor. Because Tlr4 interprets the chemical structure of an LPS molecule, we conclude that LPS must achieve close physical proximity with Tlr4 in the course of signal transduction.

Original languageEnglish (US)
Pages (from-to)2163-2167
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number5
DOIs
Publication statusPublished - Feb 29 2000

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Keywords

  • C3H/HeJ
  • Endotoxin
  • Macrophage
  • Specificity

ASJC Scopus subject areas

  • Genetics
  • General

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