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PMID: 10681462 Published · ppublish English Journal Article

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 5 ·2000-02-29 ·Pages 2163-7

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

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.

MeSH Terms
Animals Biomarkers Cells, Cultured Drosophila Proteins Genetic Complementation Test Humans Lipid A/pharmacology Lipopolysaccharides/pharmacology Macrophages/cytology,drug effects,immunology Membrane Glycoproteins/genetics,physiology Mice Mice, Inbred C3H Receptors, Cell Surface/genetics,physiology Toll-Like Receptor 4 Toll-Like Receptors
Chemicals
Biomarkers Drosophila Proteins Lipid A Lipopolysaccharides Membrane Glycoproteins Receptors, Cell Surface TLR4 protein, human Toll-Like Receptor 4 Toll-Like Receptors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Poltorak A
The Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9050, USA.
Ricciardi-Castagnoli P
Citterio S
Beutler B
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.040565397
Published
2000-02-29
Pages
2163-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC15771
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.040565397 PMC Full Text View journal details
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