Physical contact between lipopolysaccharide and Toll-like receptor 4 revealed by genetic complementation
Open Access
- 18 February 2000
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 97 (5), 2163-2167
- https://doi.org/10.1073/pnas.040565397
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.Keywords
This publication has 39 references indexed in Scilit:
- Lipopolysaccharide binding protein and soluble CD14 catalyze exchange of phospholipids.JCI Insight, 1997
- Lipopolysaccharide‐binding protein mediates CD14‐independent intercalation of lipopolysaccharide into phospholipid membranesFEBS Letters, 1996
- Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14.The Journal of Experimental Medicine, 1994
- CD14, a Receptor for Complexes of Lipopolysaccharide (LPS) and LPS Binding ProteinScience, 1990
- Structural and physicochemical requirements of endotoxins for the activation of arachidonic acid metabolism in mouse peritoneal macrophages in vitroEuropean Journal of Biochemistry, 1989
- Detoxification of Bacterial Lipopolysaccharides (Endotoxins) by a Human Neutrophil EnzymeScience, 1986
- Passive Immunization Against Cachectin/Tumor Necrosis Factor Protects Mice from Lethal Effect of EndotoxinScience, 1985
- Biological activities of analogues of lipid A based chemically on the revised structural modelEuropean Journal of Biochemistry, 1984
- Endotoxic properties of chemically synthesized lipid A part structures. Comparison of synthetic lipid A precursor and synthetic analogues with biosynthetic lipid A precursor and free lipid AEuropean Journal of Biochemistry, 1984
- The Primary Role of Lymphoreticnlar Cells in the Mediation of Host Responses to Bacterial EndotoximThe Journal of Infectious Diseases, 1980