Published Online
on October 21, 2002

A more recent version of this article appeared on November 12, 2002

This Article Full Text (PDF) All Versions of this Article: 106/20/2608    most recent 01.CIR.0000038110.69369.4Cv1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Knuefermann, P. Articles by Vallejo, J. G. Search for Related Content PubMed PubMed Citation Articles by Knuefermann, P. Articles by Vallejo, J. G. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Related Collections Contractile function Animal models of human disease

Submitted on May 21, 2002
Revised on August 14, 2002
Accepted on August 21, 2002

CD14-Deficient Mice Are Protected Against Lipopolysaccharide-Induced Cardiac Inflammation and Left Ventricular Dysfunction

Pascal Knuefermann MD, Shintaro Nemoto MD, PhD, Arunima Misra MD, Naoki Nozaki MD, Gilberto Defreitas BS, Sanna M. Goyert PhD, Blase A. Carabello MD, Douglas L. Mann MD, and Jesus G. Vallejo MD^*

From the Department of Pediatrics, Section of Infectious Diseases (J.G.V.), and Department of Medicine (P.K., A.M., N.N., D.L.M., J.G.V.), Winters Center For Heart Failure Research, Veterans Affairs Medical Center (S.N., B.A.C.), Baylor College of Medicine, Houston, Tex; and North Shore University Hospital (S.M.G.), Manhasset, NY.

^* To whom correspondence should be addressed. E-mail: jvallejo{at}bcm.tmc.edu.

Background—The molecular mechanisms responsible for sepsis-induced myocardial dysfunction remain undefined. CD14 mediates the inflammatory response to lipopolysaccharide (LPS) in various organs including the heart. In this study we investigated the role of CD14 in LPS-induced myocardial dysfunction in vivo.

Methods and Results—Wild-type and CD14-deficient (CD14-D) mice were challenged with Escherichia coli LPS. Myocardial tumor necrosis factor, interleukin-1ß (IL-1ß), and NOS2 induction was measured before and 6 hours after LPS challenge. Echocardiographic parameters of left ventricular function were measured before and 6 hours after LPS administration. LPS challenge induced a significant increase in myocardial tumor necrosis factor and IL-1ß mRNA and protein expression in wild-type mice. In contrast, mRNA and protein levels for TNF and IL-1ß were significantly blunted in CD14-D mice. An increase in NOS2 protein was noted within 6 hours of LPS provocation only in the hearts of wild-type mice. This was associated with an increase in ventricular cGMP levels. Activation of nuclear factor-B was observed within 30 minutes of LPS in the hearts of wild-type mice but not in CD14-D mice. In wild-type mice, LPS significantly decreased left ventricular fractional shortening, velocity of circumferential shortening, and dP/dt_max. LPS-treated CD14-D mice maintained normal cardiac function.

Conclusions—These results suggest that CD14 is important in mediating the proinflammatory response induced by LPS in the heart and that CD14 is necessary for the development of left ventricular dysfunction during LPS-induced shock in vivo.

Key words: immune system • shock • inflammation • echocardiography

This article has been cited by other articles:

				L. N. Jackson, L. A. Chen, S. D. Larson, S. R. Silva, P. G. Rychahou, P. J. Boor, J. Li, G. DeFreitas, W. L. Stafford, C. M. Townsend Jr., et al. Development and Characterization of a Novel In vivo Model of Carcinoid Syndrome Clin. Cancer Res., April 15, 2009; 15(8): 2747 - 2755. [Abstract] [Full Text] [PDF]

				W. Chao Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart Am J Physiol Heart Circ Physiol, January 1, 2009; 296(1): H1 - H12. [Abstract] [Full Text] [PDF]

				Y. Feng, H. Zhao, X. Xu, E. S. Buys, M. J. Raher, J. C. Bopassa, H. Thibault, M. Scherrer-Crosbie, U. Schmidt, and W. Chao Innate immune adaptor MyD88 mediates neutrophil recruitment and myocardial injury after ischemia-reperfusion in mice Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1311 - H1318. [Abstract] [Full Text] [PDF]

				J. H. Boyd, B. Kan, H. Roberts, Y. Wang, and K. R. Walley S100A8 and S100A9 Mediate Endotoxin-Induced Cardiomyocyte Dysfunction via the Receptor for Advanced Glycation End Products Circ. Res., May 23, 2008; 102(10): 1239 - 1246. [Abstract] [Full Text] [PDF]

				P. Knuefermann, M. Schwederski, M. Velten, P. Krings, H. Ehrentraut, M. Rudiger, O. Boehm, K. Fink, U. Dreiner, C. Grohe, et al. Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of Toll-like receptor 9 Cardiovasc Res, April 1, 2008; 78(1): 26 - 35. [Abstract] [Full Text] [PDF]

				S. Metkar, S. Awasthi, E. Denamur, K. S. Kim, S. C. Gangloff, S. Teichberg, A. Haziot, J. Silver, and S. M. Goyert Role of CD14 in Responses to Clinical Isolates of Escherichia coli: Effects of K1 Capsule Expression Infect. Immun., November 1, 2007; 75(11): 5415 - 5424. [Abstract] [Full Text] [PDF]

				S. Ehrentraut, S. Frede, H. Stapel, T. Mengden, C. Grohe, J. Fandrey, R. Meyer, and G. Baumgarten Antagonism of Lipopolysaccharide-Induced Blood Pressure Attenuation and Vascular Contractility Arterioscler Thromb Vasc Biol, October 1, 2007; 27(10): 2170 - 2176. [Abstract] [Full Text] [PDF]

				H. Stapel, S.-C. Kim, S. Osterkamp, P. Knuefermann, A. Hoeft, R. Meyer, C. Grohe, and G. Baumgarten Toll-like receptor 4 modulates myocardial ischaemia-reperfusion injury: Role of matrix metalloproteinases Eur J Heart Fail, November 1, 2006; 8(7): 665 - 672. [Abstract] [Full Text] [PDF]

				X. Zhu, H. Zhao, A. R. Graveline, E. S. Buys, U. Schmidt, K. D. Bloch, A. Rosenzweig, and W. Chao MyD88 and NOS2 are essential for Toll-like receptor 4-mediated survival effect in cardiomyocytes Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1900 - H1909. [Abstract] [Full Text] [PDF]

				S. Genth-Zotz, S. von Haehling, A. P. Bolger, P. R. Kalra, R. Wensel, A. J.S. Coats, H.-D. Volk, and S. D. Anker The anti-CD14 antibody IC14 suppresses ex vivo endotoxin stimulated tumor necrosis factor-alpha in patients with chronic heart failure Eur J Heart Fail, June 1, 2006; 8(4): 366 - 372. [Abstract] [Full Text] [PDF]

				W. Tao, V. T. Enoh, C. Y. Lin, W. E. Johnston, P. Li, and E. R. Sherwood Cardiovascular dysfunction caused by cecal ligation and puncture is attenuated in CD8 knockout mice treated with anti-asialoGM1 Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2005; 289(2): R478 - R485. [Abstract] [Full Text] [PDF]

				W. Chao, Y. Shen, X. Zhu, H. Zhao, M. Novikov, U. Schmidt, and A. Rosenzweig Lipopolysaccharide Improves Cardiomyocyte Survival and Function after Serum Deprivation J. Biol. Chem., June 10, 2005; 280(23): 21997 - 22005. [Abstract] [Full Text] [PDF]

				F. Chagnon, C. N. Metz, R. Bucala, and O. Lesur Endotoxin-Induced Myocardial Dysfunction: Effects of Macrophage Migration Inhibitory Factor Neutralization Circ. Res., May 27, 2005; 96(10): 1095 - 1102. [Abstract] [Full Text] [PDF]

				I. A. Sebag, M. D. Handschumacher, F. Ichinose, J. G. Morgan, R. Hataishi, A. C. T. Rodrigues, J. L. Guerrero, W. Steudel, M. J. Raher, E. F. Halpern, et al. Quantitative Assessment of Regional Myocardial Function in Mice by Tissue Doppler Imaging: Comparison With Hemodynamics and Sonomicrometry Circulation, May 24, 2005; 111(20): 2611 - 2616. [Abstract] [Full Text] [PDF]

				P. Knuefermann, Y. Sakata, J. S. Baker, C.-H. Huang, K. Sekiguchi, H. S. Hardarson, O. Takeuchi, S. Akira, and J. G. Vallejo Toll-Like Receptor 2 Mediates Staphylococcus aureus-Induced Myocardial Dysfunction and Cytokine Production in the Heart Circulation, December 14, 2004; 110(24): 3693 - 3698. [Abstract] [Full Text] [PDF]

				W. Tao and E. R. Sherwood {beta}2-Microglobulin knockout mice treated with anti-asialoGM1 exhibit improved hemodynamics and cardiac contractile function during acute intra-abdominal sepsis Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2004; 286(3): R569 - R575. [Abstract] [Full Text] [PDF]

				M.-L. Wong, F. O'Kirwan, N. Khan, J. Hannestad, K. H. Wu, D. Elashoff, G. Lawson, P. W. Gold, S. M. McCann, and J. Licinio Identification, characterization, and gene expression profiling of endotoxin-induced myocarditis PNAS, November 25, 2003; 100(24): 14241 - 14246. [Abstract] [Full Text] [PDF]

				D. de Kleijn and G. Pasterkamp Toll-like receptors in cardiovascular diseases Cardiovasc Res, October 15, 2003; 60(1): 58 - 67. [Abstract] [Full Text] [PDF]