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Research Article |
1 University of Portsmouth, School of Biological Sciences, King Henry Building,
King Henry I Street, Portsmouth, PO1 2DY, UK
2 Department of Immunology, Saga Medical School, Nabeshima, Japan
3 Boston University School of Medicine, Boston Medical Center, The Maxwell
Finland Laboratory for Infectious Diseases, Boston, Massachusetts 02118,
USA
* Present address: Department of Medicine, Division of Infectious Diseases,
University of Massachusetts Medical School, Worcester, MA 01665, USA
Author for correspondence (e-mail:
ktrian{at}hotmail.com
)
Accepted 19 March 2002
The plasma membrane of cells is composed of lateral heterogeneities,
patches and microdomains. These membrane microdomains or lipid rafts are
enriched in glycosphingolipids and cholesterol and have been implicated in
cellular processes such as membrane sorting and signal transduction. In this
study we investigated the importance of lipid raft formation in the innate
immune recognition of bacteria using biochemical and fluorescence imaging
techniques. We found that receptor molecules that are implicated in
lipopolysaccharide (LPS)-cellular activation, such as CD14, heat shock protein
(hsp) 70, 90, Chemokine receptor 4 (CXCR4), growth differentiation factor 5
(GDF5) and Toll-like receptor 4 (TLR4), are present in microdomains following
LPS stimulation. Lipid raft integrity is essential for LPS-cellular
activation, since raft-disrupting drugs, such as nystatin or MCD, inhibit
LPS-induced TNF-
secretion. Our results suggest that the entire
bacterial recognition system is based around the ligation of CD14 by bacterial
components and the recruitment of multiple signalling molecules, such as
hsp70, hsp90, CXCR4, GDF5 and TLR4, at the site of CD14-LPS ligation, within
the lipid rafts.
Key words: Lipid rafts, LPS, Heat shock proteins, CXCR4, GDF5, TLR4
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M. Triantafilou, M. Manukyan, A. Mackie, S. Morath, T. Hartung, H. Heine, and K. Triantafilou Lipoteichoic Acid and Toll-like Receptor 2 Internalization and Targeting to the Golgi Are Lipid Raft-dependent J. Biol. Chem., September 24, 2004; 279(39): 40882 - 40889. [Abstract] [Full Text] [PDF]
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M. B. Fessler, P. G. Arndt, S. C. Frasch, J. G. Lieber, C. A. Johnson, R. C. Murphy, J. A. Nick, D. L. Bratton, K. C. Malcolm, and G. S. Worthen Lipid Rafts Regulate Lipopolysaccharide-induced Activation of Cdc42 and Inflammatory Functions of the Human Neutrophil J. Biol. Chem., September 17, 2004; 279(38): 39989 - 39998. [Abstract] [Full Text] [PDF]
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A. V. Bocharov, I. N. Baranova, T. G. Vishnyakova, A. T. Remaley, G. Csako, F. Thomas, A. P. Patterson, and T. L. Eggerman Targeting of Scavenger Receptor Class B Type I by Synthetic Amphipathic {alpha}-Helical-containing Peptides Blocks Lipopolysaccharide (LPS) Uptake and LPS-induced Pro-inflammatory Cytokine Responses in THP-1 Monocyte Cells J. Biol. Chem., August 20, 2004; 279(34): 36072 - 36082. [Abstract] [Full Text] [PDF]
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S. B. Pruett, C. Schwab, Q. Zheng, and R. Fan Suppression of Innate Immunity by Acute Ethanol Administration: A Global Perspective and a New Mechanism Beginning with Inhibition of Signaling through TLR3 J. Immunol., August 15, 2004; 173(4): 2715 - 2724. [Abstract] [Full Text] [PDF]
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J. A. Whitsett, C. J. Bachurski, K. C. Barnes, P. A. Bunn Jr., L. M. Case, D. N. Cook, D. Crooks, M. W. Duncan, L. Dwyer-Nield, R. C. Elston, et al. Functional Genomics of Lung Disease Am. J. Respir. Cell Mol. Biol., August 1, 2004; 31(2/S1): S1 - S81. [Full Text] [PDF]
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S. Jaksits, W. Bauer, E. Kriehuber, M. Zeyda, T. M. Stulnig, G. Stingl, E. Fiebiger, and D. Maurer Lipid Raft-Associated GTPase Signaling Controls Morphology and CD8+ T Cell Stimulatory Capacity of Human Dendritic Cells J. Immunol., August 1, 2004; 173(3): 1628 - 1639. [Abstract] [Full Text] [PDF]
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S. Dunzendorfer, H.-K. Lee, K. Soldau, and P. S. Tobias TLR4 Is the Signaling but Not the Lipopolysaccharide Uptake Receptor J. Immunol., July 15, 2004; 173(2): 1166 - 1170. [Abstract] [Full Text] [PDF]
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H. Fang, R. A. Pengal, X. Cao, L. P. Ganesan, M. D. Wewers, C. B. Marsh, and S. Tridandapani Lipopolysaccharide-Induced Macrophage Inflammatory Response Is Regulated by SHIP J. Immunol., July 1, 2004; 173(1): 360 - 366. [Abstract] [Full Text] [PDF]
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J. J. Rose, J. F. Foley, P. M. Murphy, and S. Venkatesan On the Mechanism and Significance of Ligand-induced Internalization of Human Neutrophil Chemokine Receptors CXCR1 and CXCR2 J. Biol. Chem., June 4, 2004; 279(23): 24372 - 24386. [Abstract] [Full Text] [PDF]
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J. Y. Lee, L. Zhao, H. S. Youn, A. R. Weatherill, R. Tapping, L. Feng, W. H. Lee, K. A. Fitzgerald, and D. H. Hwang Saturated Fatty Acid Activates but Polyunsaturated Fatty Acid Inhibits Toll-like Receptor 2 Dimerized with Toll-like Receptor 6 or 1 J. Biol. Chem., April 23, 2004; 279(17): 16971 - 16979. [Abstract] [Full Text] [PDF]
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P. G. Arndt, N. Suzuki, N. J. Avdi, K. C. Malcolm, and G. S. Worthen Lipopolysaccharide-induced c-Jun NH2-terminal Kinase Activation in Human Neutrophils: ROLE OF PHOSPHATIDYLINOSITOL 3-KINASE AND Syk-MEDIATED PATHWAYS J. Biol. Chem., March 19, 2004; 279(12): 10883 - 10891. [Abstract] [Full Text] [PDF]
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 C. Gomez-Mouton, R. A. Lacalle, E. Mira, S. Jimenez-Baranda, D. F. Barber, A. C. Carrera, C. Martinez-A., and S. Manes Dynamic redistribution of raft domains as an organizing platform for signaling during cell chemotaxis J. Cell Biol., March 1, 2004; 164(5): 759 - 768. [Abstract] [Full Text] [PDF]
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A. A. Cecil and M. J. Klemsz p38 activation through Toll-like receptors modulates IFN-{gamma}-induced expression of the Tap-1 gene only in macrophages J. Leukoc. Biol., March 1, 2004; 75(3): 560 - 568. [Abstract] [Full Text] [PDF]
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R. G. Khadaroo, A. Kapus, K. A. Powers, M. I. Cybulsky, J. C. Marshall, and O. D. Rotstein Oxidative Stress Reprograms Lipopolysaccharide Signaling via Src Kinase-dependent Pathway in RAW 264.7 Macrophage Cell Line J. Biol. Chem., November 28, 2003; 278(48): 47834 - 47841. [Abstract] [Full Text] [PDF]
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M. W. Hornef, B. H. Normark, A. Vandewalle, and S. Normark Intracellular Recognition of Lipopolysaccharide by Toll-like Receptor 4 in Intestinal Epithelial Cells J. Exp. Med., October 20, 2003; 198(8): 1225 - 1235. [Abstract] [Full Text] [PDF]
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M. Triantafilou and K. Triantafilou Receptor cluster formation during activation by bacterial products Innate Immunity, October 1, 2003; 9(5): 331 - 335. [Abstract] [PDF]
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K. Sau, S. S. Mambula, E. Latz, P. Henneke, D. T. Golenbock, and S. M. Levitz The Antifungal Drug Amphotericin B Promotes Inflammatory Cytokine Release by a Toll-like Receptor- and CD14-dependent Mechanism J. Biol. Chem., September 26, 2003; 278(39): 37561 - 37568. [Abstract] [Full Text] [PDF]
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J. Stebbing, B. Gazzard, S. Portsmouth, F. Gotch, L. Kim, M. Bower, S. Mandalia, R. Binder, P. Srivastava, and S. Patterson Disease-associated dendritic cells respond to disease-specific antigens through the common heat shock protein receptor Blood, September 1, 2003; 102(5): 1806 - 1814. [Abstract] [Full Text] [PDF]
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N. Mackman How Do Oxidized Phospholipids Inhibit LPS Signaling? Arterioscler Thromb Vasc Biol, July 1, 2003; 23(7): 1133 - 1136. [Full Text] [PDF]
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K. A. Walton, A. L. Cole, M. Yeh, G. Subbanagounder, S. R. Krutzik, R. L. Modlin, R. M. Lucas, J. Nakai, E. J. Smart, D. K. Vora, et al. Specific Phospholipid Oxidation Products Inhibit Ligand Activation of Toll-Like Receptors 4 and 2 Arterioscler Thromb Vasc Biol, July 1, 2003; 23(7): 1197 - 1203. [Abstract] [Full Text] [PDF]
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A. H. Broquet, G. Thomas, J. Masliah, G. Trugnan, and M. Bachelet Expression of the Molecular Chaperone Hsp70 in Detergent-resistant Microdomains Correlates with Its Membrane Delivery and Release J. Biol. Chem., June 6, 2003; 278(24): 21601 - 21606. [Abstract] [Full Text] [PDF]
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A. Gross, M. Bouaboula, P. Casellas, J.-P. Liautard, and J. Dornand Subversion and Utilization of the Host Cell Cyclic Adenosine 5'-Monophosphate/Protein Kinase A Pathway by Brucella During Macrophage Infection J. Immunol., June 1, 2003; 170(11): 5607 - 5614. [Abstract] [Full Text] [PDF]
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P. Forsythe and A. D. Befus CCR3: A Key to Mast Cell Phenotypic and Functional Diversity? Am. J. Respir. Cell Mol. Biol., April 1, 2003; 28(4): 405 - 409. [Full Text] [PDF]
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E. Latz, A. Visintin, E. Lien, K. A. Fitzgerald, B. G. Monks, E. A. Kurt-Jones, D. T. Golenbock, and T. Espevik Lipopolysaccharide Rapidly Traffics to and from the Golgi Apparatus with the Toll-like Receptor 4-MD-2-CD14 Complex in a Process That Is Distinct from the Initiation of Signal Transduction J. Biol. Chem., November 27, 2002; 277(49): 47834 - 47843. [Abstract] [Full Text] [PDF]
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K. Guillemin, N. R. Salama, L. S. Tompkins, and S. Falkow Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection PNAS, November 12, 2002; 99(23): 15136 - 15141. [Abstract] [Full Text] [PDF]
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A. A. Waheed and T. L. Z. Jones Hsp90 Interactions and Acylation Target the G Protein Galpha 12 but Not Galpha 13 to Lipid Rafts J. Biol. Chem., August 30, 2002; 277(36): 32409 - 32412. [Abstract] [Full Text] [PDF]
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