Chemokine receptor 4 (CXCR4) is part of the lipopolysaccharide "sensing apparatus".
Recognition of bacterial lipopolysaccharide (LPS) by the innate immune system involves at least three receptor molecules: CD14, TLR4 and MD-2. Additional receptor components such as heat shock proteins, chemokine receptor 4 (CXCR4), or CD55 have been suggested to be part of this activation cluster; possibly acting as additional LPS transfer molecules. Our group has previously identified CXCR4 as a component of the "LPS-sensing apparatus". In this study we aimed to elucidate the role that CXCR4 plays in innate immune responses to LPS. Here we demonstrate that CXCR4 transfection results in responsiveness to LPS. Fluorescence correlation spectroscopy experiments further showed that LPS directly interacts with CXCR4. Our data suggest that CXCR4 is not only involved in LPS binding but is also responsible for triggering signalling, especially mitogen-activated protein kinases in response to LPS. Finally, co-clustering of CXCR4 with other LPS receptors seems to be crucial for LPS signalling, thus suggesting that CXCR4 is a functional part of the multimeric LPS "sensing apparatus".
Triantafilou
Martha
M
Infection and Immunity Group, School of Life Sciences, University of Sussex, Falmer, Brighton, UK.
Lepper
Philipp M
PM
Briault
Caspar David
CD
Ahmed
Mohamed Abd Elrahman
MA
Dmochowski
Josh M
JM
Schumann
Christian
C
Triantafilou
Kathy
K
D015153:Blotting, Western; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology*; D018613:Microscopy, Confocal; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D014162:Transfection
D008070:Lipopolysaccharides; D019718:Receptors, CXCR4; D020928:Mitogen-Activated Protein Kinases