| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Department of Infectious Diseases, Tropical Medicine, and AIDS, and
Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands;
ICOS Corporation, Bothell, WA; and
¶ Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
CD14 is a receptor for cell wall components of Gram-negative and Gram-positive bacteria that has been implicated in the initiation of the inflammatory response to sepsis. To determine the role of CD14 in LPS-induced effects in humans, 16 healthy subjects received an i.v. injection of LPS (4 ng/kg) preceded (-2 h) by i.v. IC14, a recombinant chimeric mAb against human CD14, at a dose of 1 mg/kg over 1 h, or placebo. In subjects receiving IC14, saturation of CD14 on circulating monocytes and granulocytes was >90% at the time of LPS injection. IC14 attenuated LPS-induced clinical symptoms and strongly inhibited LPS-induced proinflammatory cytokine release, while only delaying the release of the anti-inflammatory cytokines soluble TNF receptor type I and IL-1 receptor antagonist. IC14 also inhibited leukocyte activation, but more modestly reduced endothelial cell activation and the acute phase protein response. The capacity of circulating monocytes and granulocytes to phagocytose Escherichia coli was only marginally reduced after infusion of IC14. These data provide the first proof of principle that blockade of CD14 is associated with reduced LPS responsiveness in humans in vivo.
This article has been cited by other articles:
|
|
 |
|
  R. Fernandez, S. Gonzalez, S. Rey, P. P. Cortes, K. R. Maisey, E.-P. Reyes, C. Larrain, and P. Zapata Lipopolysaccharide-induced carotid body inflammation in cats: functional manifestations, histopathology and involvement of tumour necrosis factor-{alpha} Exp Physiol, July 1, 2008; 93(7): 892 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. van 't Veer, P. S. van den Pangaart, M. A. D. van Zoelen, M. de Kruif, R. S. Birjmohun, E. S. Stroes, A. F. de Vos, and T. van der Poll Induction of IRAK-M Is Associated with Lipopolysaccharide Tolerance in a Human Endotoxemia Model J. Immunol., November 15, 2007; 179(10): 7110 - 7120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Daubeuf, J. Mathison, S. Spiller, S. Hugues, S. Herren, W. Ferlin, M. Kosco-Vilbois, H. Wagner, C. J. Kirschning, R. Ulevitch, et al. TLR4/MD-2 Monoclonal Antibody Therapy Affords Protection in Experimental Models of Septic Shock J. Immunol., November 1, 2007; 179(9): 6107 - 6114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bahador and A. S. Cross Review: From therapy to experimental model: a hundred years of endotoxin administration to human subjects Innate Immunity, October 1, 2007; 13(5): 251 - 279. [Abstract] [PDF]
|
|
|
|
 |
|
 V. Poulaki, E. Iliaki, N. Mitsiades, C. S. Mitsiades, Y. N. Paulus, D. V. Bula, E. S. Gragoudas, and J. W. Miller Inhibition of Hsp90 attenuates inflammation in endotoxin-induced uveitis FASEB J, July 1, 2007; 21(9): 2113 - 2123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Knapp, U. Matt, N. Leitinger, and T. van der Poll Oxidized Phospholipids Inhibit Phagocytosis and Impair Outcome in Gram-Negative Sepsis In Vivo J. Immunol., January 15, 2007; 178(2): 993 - 1001. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Chen, D. B. Rosenbluth, M. A. Mintun, and D. P. Schuster FDG-PET imaging of pulmonary inflammation in healthy volunteers after airway instillation of endotoxin J Appl Physiol, May 1, 2006; 100(5): 1602 - 1609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Knapp, S. Gibot, A. de Vos, H. H. Versteeg, M. Colonna, and T. van der Poll Cutting Edge: Expression Patterns of Surface and Soluble Triggering Receptor Expressed on Myeloid Cells-1 in Human Endotoxemia J. Immunol., December 15, 2004; 173(12): 7131 - 7134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Renckens, S. Weijer, A. F. de Vos, J. M. Pater, J. C. Meijers, C. E. Hack, M. Levi, and T. van der Poll Inhibition of Plasmin Activity by Tranexamic Acid Does Not Influence Inflammatory Pathways During Human Endotoxemia Arterioscler. Thromb. Vasc. Biol., March 1, 2004; 24(3): 483 - 488. [Abstract] [Full Text]
|
|
|
|
|
|
T. Axtelle and J. Pribble An overview of clinical studies in healthy subjects and patients with severe sepsis with IC14, a CD14-specific chimeric monoclonal antibody Innate Immunity, December 1, 2003; 9(6): 385 - 389. [Abstract] [PDF]
|
|
|
|
 |
|
 E. Eldering, C. A. Spek, H. L. Aberson, A. Grummels, I. A. Derks, A. F. de Vos, C. J. McElgunn, and J. P. Schouten Expression profiling via novel multiplex assay allows rapid assessment of gene regulation in defined signalling pathways Nucleic Acids Res., December 1, 2003; 31(23): e153 - e153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Weijer, M. E. Sewnath, A. F. de Vos, S. Florquin, K. van der Sluis, D. J. Gouma, K. Takeda, S. Akira, and T. van der Poll Interleukin-18 Facilitates the Early Antimicrobial Host Response to Escherichia coli Peritonitis Infect. Immun., October 1, 2003; 71(10): 5488 - 5497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Branger, B. van den Blink, S. Weijer, A. Gupta, S. J.H. van Deventer, C. E. Hack, M. P. Peppelenbosch, and T. van der Poll Inhibition of coagulation, fibrinolysis, and endothelial cell activation by a p38 mitogen-activated protein kinase inhibitor during human endotoxemia Blood, June 1, 2003; 101(11): 4446 - 4448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. C. Aird The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome Blood, May 15, 2003; 101(10): 3765 - 3777. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Knuefermann, S. Nemoto, A. Misra, N. Nozaki, G. Defreitas, S. M. Goyert, B. A. Carabello, D. L. Mann, and J. G. Vallejo CD14-Deficient Mice Are Protected Against Lipopolysaccharide-Induced Cardiac Inflammation and Left Ventricular Dysfunction Circulation, November 12, 2002; 106(20): 2608 - 2615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Hintz, A. J. Rassias, K. Wardwell, M. L. Moss, P. M. Morganelli, P. A. Pioli, A. L. Givan, P. K. Wallace, M. P. Yeager, and P. M. Guyre Endotoxin induces rapid metalloproteinase-mediated shedding followed by up-regulation of the monocyte hemoglobin scavenger receptor CD163 J. Leukoc. Biol., October 1, 2002; 72(4): 711 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Ishida, H. Kubo, S. Suzuki, T. Suzuki, S. Akashi, K. Inoue, S. Maeda, H. Kikuchi, H. Sasaki, and T. Kondo Hypoxia Diminishes Toll-Like Receptor 4 Expression Through Reactive Oxygen Species Generated by Mitochondria in Endothelial Cells J. Immunol., August 15, 2002; 169(4): 2069 - 2075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Yan, W. Al-Hertani, D. Byers, and R. Bortolussi Lipopolysaccharide-Binding Protein- and CD14-Dependent Activation of Mitogen-Activated Protein Kinase p38 by Lipopolysaccharide in Human Neutrophils Is Associated with Priming of Respiratory Burst Infect. Immun., August 1, 2002; 70(8): 4068 - 4074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. K. Varma, C. Y. Lin, T. E. Toliver-Kinsky, and E. R. Sherwood Endotoxin-Induced Gamma Interferon Production: Contributing Cell Types and Key Regulatory Factors Clin. Vaccine Immunol., May 1, 2002; 9(3): 530 - 543. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
