| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Maxwell Finland Laboratory for Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, MA 02118;
Eisai Research Institute, Andover, MA 01810;
Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02118; and
§
Norwegian University of Science and Technology, Trondheim, Norway
The activation of phagocytes by the lipid A moiety of LPS has been implicated in the pathogenesis of Gram-negative sepsis. While two LPS receptors, CD14 and CD11/CD18, have been associated with cell signaling, details of the LPS signal transduction cascade remain obscure. CD14, which exists as a GPI-anchored and a soluble protein, lacks cytoplasmic-signaling domains, suggesting that an ancillary molecule is required to activate cells. The CD11/CD18 integrins are transmembrane proteins. Like CD14, they are capable of mediating LPS-induced cellular activation when expressed on the surface of hamster fibroblasts Chinese hamster ovary (CHO)-K1. The observation that a cytoplasmic deletion mutant is still capable of activating transfected CHO-K1 argues that CD11/CD18 also utilizes an associated signal transducer. We sought to identify further similarities between the signaling systems utilized by CD14 and CD11/CD18. LPS-binding protein, which transfers LPS to CD14, enhanced both LPS-induced cellular activation and binding of Gram-negative bacteria in CD11/CD18-transfected CHO-K1, thus implying that LPS-binding protein can also transfer LPS to CD11/CD18. When synthetic lipid A analogues were analyzed for their ability to function as LPS agonists, or antagonists, in the CHO transfectants, we found the effects were identical regardless of which LPS receptor was expressed. This supports the hypothesis that a receptor distinct from CD14 and CD11/CD18 is responsible for discriminating between the lipid A of LPS and the LPS antagonists. We propose that this receptor, which is the target of the LPS antagonists, functions as the true signal transducer in LPS-induced cellular activation for both CD14 and CD11/CD18.
This article has been cited by other articles:
|
|
 |
|
  C. R. Oliva, M. K. Swiecki, C. E. Griguer, M. W. Lisanby, D. C. Bullard, C. L. Turnbough Jr., and J. F. Kearney The integrin Mac-1 (CR3) mediates internalization and directs Bacillus anthracis spores into professional phagocytes PNAS, January 29, 2008; 105(4): 1261 - 1266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Schreiter, M Hausmann, T Spoettl, U G Strauch, F Bataille, J Schoelmerich, H Herfarth, W Falk, and G Rogler Glycoprotein (gp) 96 expression: induced during differentiation of intestinal macrophages but impaired in Crohn's disease Gut, July 1, 2005; 54(7): 935 - 943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Heinzelmann and H. Bosshart Heparin Binds to Lipopolysaccharide (LPS)-Binding Protein, Facilitates the Transfer of LPS to CD14, and Enhances LPS-Induced Activation of Peripheral Blood Monocytes J. Immunol., February 15, 2005; 174(4): 2280 - 2287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Epelman, D. Stack, C. Bell, E. Wong, G. G. Neely, S. Krutzik, K. Miyake, P. Kubes, L. D. Zbytnuik, L. L. Ma, et al. Different Domains of Pseudomonas aeruginosa Exoenzyme S Activate Distinct TLRs J. Immunol., August 1, 2004; 173(3): 2031 - 2040. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Hongkuan Fan and J. A. Cook Review: Molecular mechanisms of endotoxin tolerance Innate Immunity, April 1, 2004; 10(2): 71 - 84. [Abstract] [PDF]
|
|
|
|
|
|
Brazilian National Genome Project Consortium:, A. T. Ribeiro de Vasconcelos, D. F. de Almeida, M. Hungria, C. T. Guimaraes, R. V. Antonio, F. C. Almeida, L. G. P. de Almeida, R. de Almeida, J. A. Alves-Gomes, et al. The complete genome sequence of Chromobacterium violaceum reveals remarkable and exploitable bacterial adaptability PNAS, September 30, 2003; 100(20): 11660 - 11665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Qureshi, P.-Y. Perera, J. Shen, G. Zhang, A. Lenschat, G. Splitter, D. C. Morrison, and S. N. Vogel The Proteasome as a Lipopolysaccharide-Binding Protein in Macrophages: Differential Effects of Proteasome Inhibition on Lipopolysaccharide-Induced Signaling Events J. Immunol., August 1, 2003; 171(3): 1515 - 1525. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Van Amersfoort, T. J. C. Van Berkel, and J. Kuiper Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock Clin. Microbiol. Rev., July 1, 2003; 16(3): 379 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Bosshart and M. Heinzelmann Arginine-Rich Cationic Polypeptides Amplify Lipopolysaccharide-Induced Monocyte Activation Infect. Immun., December 1, 2002; 70(12): 6904 - 6910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Henneke, O. Takeuchi, R. Malley, E. Lien, R. R. Ingalls, M. W. Freeman, T. Mayadas, V. Nizet, S. Akira, D. L. Kasper, et al. Cellular Activation, Phagocytosis, and Bactericidal Activity Against Group B Streptococcus Involve Parallel Myeloid Differentiation Factor 88-Dependent and Independent Signaling Pathways J. Immunol., October 1, 2002; 169(7): 3970 - 3977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Monick, L. Powers, N. Butler, T. Yarovinsky, and G. W. Hunninghake Interaction of matrix with integrin receptors is required for optimal LPS-induced MAP kinase activation Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L390 - L402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.M. Monick and G.W. Hunninghake Activation of second messenger pathways in alveolar macrophages by endotoxin Eur. Respir. J., July 1, 2002; 20(1): 210 - 222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Hajishengallis, M. Martin, H. T. Sojar, A. Sharma, R. E. Schifferle, E. DeNardin, M. W. Russell, and R. J. Genco Dependence of Bacterial Protein Adhesins on Toll-Like Receptors for Proinflammatory Cytokine Induction Clin. Vaccine Immunol., March 1, 2002; 9(2): 403 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Massari, P. Henneke, Y. Ho, E. Latz, D. T. Golenbock, and L. M. Wetzler Cutting Edge: Immune Stimulation by Neisserial Porins Is Toll-Like Receptor 2 and MyD88 Dependent J. Immunol., February 15, 2002; 168(4): 1533 - 1537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Diks, S. J.H. van Deventer, and M. P. Peppelenbosch Invited review: Lipopolysaccharide recognition, internalisation, signalling and other cellular effects Innate Immunity, October 1, 2001; 7(5): 335 - 348. [Abstract] [PDF]
|
|
|
|
|
|
C. Alexander and E. Th. Rietschel Invited review: Bacterial lipopolysaccharides and innate immunity Innate Immunity, June 1, 2001; 7(3): 167 - 202. [Abstract] [PDF]
|
|
|
|
|
|
R. R. Ingalls, E. Lien, and D. T. Golenbock Membrane-Associated Proteins of a Lipopolysaccharide-Deficient Mutant of Neisseria meningitidis Activate the Inflammatory Response through Toll-Like Receptor 2 Infect. Immun., April 1, 2001; 69(4): 2230 - 2236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. H. Flo, L. Ryan, L. Kilaas, G. Skjak-Brak, R. R. Ingalls, A. Sundan, D. T. Golenbock, and T. Espevik Involvement of CD14 and beta 2-Integrins in Activating Cells with Soluble and Particulate Lipopolysaccharides and Mannuronic Acid Polymers Infect. Immun., December 1, 2000; 68(12): 6770 - 6776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Moore, L. P. Andersson, R. R. Ingalls, B. G. Monks, R. Li, M. A. Arnaout, D. T. Golenbock, and M. W. Freeman Divergent Response to LPS and Bacteria in CD14-Deficient Murine Macrophages J. Immunol., October 15, 2000; 165(8): 4272 - 4280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Wagner and R. A. Roth Neutrophil Migration Mechanisms, with an Emphasis on the Pulmonary Vasculature Pharmacol. Rev., September 1, 2000; 52(3): 349 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Mokuno, T. Matsuguchi, M. Takano, H. Nishimura, J. Washizu, T. Ogawa, O. Takeuchi, S. Akira, Y. Nimura, and Y. Yoshikai Expression of Toll-Like Receptor 2 on {gamma}{delta} T Cells Bearing Invariant V{gamma}6/V{delta}1 Induced by Escherichia coli Infection in Mice J. Immunol., July 15, 2000; 165(2): 931 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. H. Flo, O. Halaas, E. Lien, L. Ryan, G. Teti, D. T. Golenbock, A. Sundan, and T. Espevik Human Toll-Like Receptor 2 Mediates Monocyte Activation by Listeria monocytogenes, But Not by Group B Streptococci or Lipopolysaccharide J. Immunol., February 15, 2000; 164(4): 2064 - 2069. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Matsuguchi, K. Takagi, T. Musikacharoen, and Y. Yoshikai Gene expressions of lipopolysaccharide receptors, toll-like receptors 2 and 4, are differently regulated in mouse T lymphocytes Blood, February 15, 2000; 95(4): 1378 - 1385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Cario, I. M. Rosenberg, S. L. Brandwein, P. L. Beck, H.-C. Reinecker, and D. K. Podolsky Lipopolysaccharide Activates Distinct Signaling Pathways in Intestinal Epithelial Cell Lines Expressing Toll-Like Receptors J. Immunol., January 15, 2000; 164(2): 966 - 972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R. Ingalls, B. G. Monks, and D. T. Golenbock Surface presentation of LPS is sufficient for initiation of signaling events Innate Immunity, August 1, 1999; 5(4): 244 - 248. [Abstract] [PDF]
|
|
|
|
|
|
N. Bhat, P.-Y. Perera, J. M. Carboni, J. Blanco, D. T. Golenbock, T. N. Mayadas, and S. N. Vogel Use of a Photoactivatable Taxol Analogue to Identify Unique Cellular Targets in Murine Macrophages: Identification of Murine CD18 as a Major Taxol-Binding Protein and a Role for Mac-1 in Taxol-Induced Gene Expression J. Immunol., June 15, 1999; 162(12): 7335 - 7342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Ingalls, B. G. Monks, and D. T. Golenbock Membrane Expression of Soluble Endotoxin-binding Proteins Permits Lipopolysaccharide Signaling in Chinese Hamster Ovary Fibroblasts Independently of CD14 J. Biol. Chem., May 14, 1999; 274(20): 13993 - 13998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Lien, J. C. Chow, L. D. Hawkins, P. D. McGuinness, K. Miyake, T. Espevik, F. Gusovsky, and D. T. Golenbock A Novel Synthetic Acyclic Lipid A-like Agonist Activates Cells via the Lipopolysaccharide/Toll-like Receptor 4 Signaling Pathway J. Biol. Chem., January 12, 2001; 276(3): 1873 - 1880. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
