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*
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037;
Department of Immunology, Saga Medical School, Nabeshima, Saga, Japan; and
Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080
Two members of the mammalian Toll-like receptor (TLR) family, TLR2 and TLR4, have been implicated as receptors mediating cellular activation in response to bacterial LPS. Through the use of mAbs raised against human TLR2 and TLR4, we have conducted studies in human cell lines and whole blood to ascertain the relative contribution of these receptors to LPS induced cytokine release. We show that the contribution of TLR2 and TLR4 to LPS-induced cellular activation correlates with the relative expression levels of these two TLRs in a given cell type. In addition, we have found that significant differences in cell stimulatory activity exist between various smooth and rough LPS types that cannot be ascribed to known LPS structural features. These results suggest that impurities in the LPS may be responsible for some of the activity and this would be in agreement with recently published results of others. Upon repurification, none of the commercial LPS preparations activate cells through TLR2, but continue to stimulate cells with comparable activity through TLR4. Our results confirm recent findings that TLR4, but not TLR2, mediates cellular activation in response to LPS derived from both Escherichia coli and Salmonella minnesota. Additionally, we show that TLR4 is the predominant signaling receptor for LPS in human whole blood.
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M. D. Lehner, F. Schwoebel, A. Kotlyarov, M. Leist, M. Gaestel, and T. Hartung Mitogen-Activated Protein Kinase-Activated Protein Kinase 2-Deficient Mice Show Increased Susceptibility to Listeria monocytogenes Infection J. Immunol., May 1, 2002; 168(9): 4667 - 4673. [Abstract] [Full Text] [PDF]
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H.-K. Lee, J. Lee, and P. S. Tobias Two Lipoproteins Extracted from Escherichia coli K-12 LCD25 Lipopolysaccharide Are the Major Components Responsible for Toll-Like Receptor 2-Mediated Signaling J. Immunol., April 15, 2002; 168(8): 4012 - 4017. [Abstract] [Full Text] [PDF]
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R. Berner, B. Furll, F. Stelter, J. Drose, H.-P. Muller, and C. Schutt Elevated Levels of Lipopolysaccharide-Binding Protein and Soluble CD14 in Plasma in Neonatal Early-Onset Sepsis Clin. Vaccine Immunol., March 1, 2002; 9(2): 440 - 445. [Abstract] [Full Text] [PDF]
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A. Yoshimura, T. Kaneko, Y. Kato, D. T. Golenbock, and Y. Hara Lipopolysaccharides from Periodontopathic Bacteria Porphyromonas gingivalis and Capnocytophaga ochracea Are Antagonists for Human Toll-Like Receptor 4 Infect. Immun., January 1, 2002; 70(1): 218 - 225. [Abstract] [Full Text] [PDF]
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 C. Li, Y. Wang, L. Gao, J. Zhang, J. Shao, S. Wang, W. Feng, X. Wang, M. Li, and Z. Chang Expression of Toll-like Receptors 2 and 4 and CD14 during Differentiation of HL-60 Cells Induced by Phorbol 12-Myristate 13-Acetate and 1{alpha}, 25-Dihydroxy-Vitamin D3 Cell Growth Differ., January 1, 2002; 13(1): 27 - 38. [Abstract] [Full Text] [PDF]
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R. M. Wooten, Y. Ma, R. A. Yoder, J. P. Brown, J. H. Weis, J. F. Zachary, C. J. Kirschning, and J. J. Weis Toll-Like Receptor 2 Is Required for Innate, But Not Acquired, Host Defense to Borrelia burgdorferi J. Immunol., January 1, 2002; 168(1): 348 - 355. [Abstract] [Full Text] [PDF]
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E. Cario, D. Brown, M. McKee, K. Lynch-Devaney, G. Gerken, and D. K. Podolsky Commensal-Associated Molecular Patterns Induce Selective Toll-Like Receptor-Trafficking from Apical Membrane to Cytoplasmic Compartments in Polarized Intestinal Epithelium Am. J. Pathol., January 1, 2002; 160(1): 165 - 173. [Abstract] [Full Text] [PDF]
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S. O. Kim, K. Ono, and J. Han Apoptosis by pan-caspase inhibitors in lipopolysaccharide-activated macrophages Am J Physiol Lung Cell Mol Physiol, November 1, 2001; 281(5): L1095 - L1105. [Abstract] [Full Text] [PDF]
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M. Martin, J. Katz, S. N. Vogel, and S. M. Michalek Differential Induction of Endotoxin Tolerance by Lipopolysaccharides Derived from Porphyromonas gingivalis and Escherichia coli J. Immunol., November 1, 2001; 167(9): 5278 - 5285. [Abstract] [Full Text] [PDF]
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A. O. Aliprantis, D. S. Weiss, J. D. Radolf, and A. Zychlinsky Release of Toll-Like Receptor-2-Activating Bacterial Lipoproteins in Shigella flexneri Culture Supernatants Infect. Immun., October 1, 2001; 69(10): 6248 - 6255. [Abstract] [Full Text] [PDF]
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G. M. Scholz, S. D. Hartson, K. Cartledge, L. Volk, R. L. Matts, and A. R. Dunn The Molecular Chaperone Hsp90 Is Required for Signal Transduction by Wild-Type Hck and Maintenance of Its Constitutively Active Counterpart Cell Growth Differ., August 1, 2001; 12(8): 409 - 417. [Abstract] [Full Text] [PDF]
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H.-H. Mu, A. D. Sawitzke, and B. C. Cole Presence of Lpsd Mutation Influences Cytokine Regulation In Vivo by the Mycoplasma arthritidis Mitogen Superantigen and Lethal Toxicity in Mice Infected with M. arthritidis Infect. Immun., June 1, 2001; 69(6): 3837 - 3844. [Abstract] [Full Text] [PDF]
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S. Vogel, M. J. Hirschfeld, and P.-Y. Perera Signal integration in lipopolysaccharide (LPS)-stimulated murine macrophages Innate Immunity, June 1, 2001; 7(3): 237 - 241. [Abstract] [PDF]
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P. Muenzner, M. Naumann, T. F. Meyer, and S. D. Gray-Owen Pathogenic Neisseria Trigger Expression of Their Carcinoembryonic Antigen-related Cellular Adhesion Molecule 1 (CEACAM1; Previously CD66a) Receptor on Primary Endothelial Cells by Activating the Immediate Early Response Transcription Factor, Nuclear Factor-kappa B J. Biol. Chem., June 22, 2001; 276(26): 24331 - 24340. [Abstract] [Full Text] [PDF]
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J. da Silva Correia, K. Soldau, U. Christen, P. S. Tobias, and R. J. Ulevitch Lipopolysaccharide Is in Close Proximity to Each of the Proteins in Its Membrane Receptor Complex. TRANSFER FROM CD14 TO TLR4 AND MD-2 J. Biol. Chem., June 8, 2001; 276(24): 21129 - 21135. [Abstract] [Full Text] [PDF]
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S. Sanlioglu, C. M. Williams, L. Samavati, N. S. Butler, G. Wang, P. B. McCray Jr., T. C. Ritchie, G. W. Hunninghake, E. Zandi, and J. F. Engelhardt Lipopolysaccharide Induces Rac1-dependent Reactive Oxygen Species Formation and Coordinates Tumor Necrosis Factor-alpha Secretion through IKK Regulation of NF-kappa B J. Biol. Chem., August 3, 2001; 276(32): 30188 - 30198. [Abstract] [Full Text] [PDF]
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S. Viriyakosol, P. S. Tobias, R. L. Kitchens, and T. N. Kirkland MD-2 Binds to Bacterial Lipopolysaccharide J. Biol. Chem., October 5, 2001; 276(41): 38044 - 38051. [Abstract] [Full Text] [PDF]
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