HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/2/H800    most recent 00701.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Tavener, S. A. Articles by Kubes, P. Search for Related Content PubMed PubMed Citation Articles by Tavener, S. A. Articles by Kubes, P.

Cellular and molecular mechanisms underlying LPS-associated myocyte impairment

Department of Physiology and Biophysics, Immunology Research Group, University of Calgary Medical Centre, Calgary, Alberta, Canada

Submitted 28 June 2005 ; accepted in final form 9 September 2005

Recently we reported that Toll-like receptor 4 (TLR4)-positive immune cells of unknown identity were responsible for the LPS-induced depression of cardiac myocyte shortening. The aim of this study is to identify the TLR4-positive cell type that is responsible for the LPS-induced cardiac dysfunction. Neither neutrophil depletion alone nor mast cell deficiency had any impact on the impairment of myocyte shortening during LPS treatment. In contrast, LPS-treated, macrophage-deficient mice demonstrated a partial reduction in shortening compared with saline-treated, macrophage-deficient mice. Because the removal of macrophages could only partially restore myocyte shortening, we also investigated the effects of removing both neutrophils and macrophages on myocyte shortening. Interestingly, endotoxemic, neutrophil-depleted, and macrophage-deficient mice had completely restored myocyte shortening. Because both macrophages and neutrophils can produce nitric oxide (NO) and TNF-, we examined LPS-treated inducible NO synthase knockout (iNOSKO) mice and TNF receptor (TNFR)-deficient mice. Eliminating both TNFR1 and TNFR2 was required to restore myocyte shortening during LPS treatment, whereas iNOS deficiency had no effect. These data suggest that macrophages and to a lesser degree neutrophils cause cardiac impairment, presumably via TNF-.

neutrophils; mast cells; macrophages; endotoxemia; tumor necrosis factor-

This article has been cited by other articles:

				M. Yang, J. Wu, C. M. Martin, P. R. Kvietys, and T. Rui Important role of p38 MAP kinase/NF-{kappa}B signaling pathway in the sepsis-induced conversion of cardiac myocytes to a proinflammatory phenotype Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H994 - H1001. [Abstract] [Full Text] [PDF]

				M. Wang, T. Markel, P. Crisostomo, C. Herring, K. K. Meldrum, K. D. Lillemoe, and D. R. Meldrum Deficiency of TNFR1 protects myocardium through SOCS3 and IL-6 but not p38 MAPK or IL-1beta Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1694 - H1699. [Abstract] [Full Text] [PDF]

				J. H. Boyd, S. Mathur, Y. Wang, R. M. Bateman, and K. R. Walley Toll-like receptor stimulation in cardiomyoctes decreases contractility and initiates an NF-{kappa}B dependent inflammatory response Cardiovasc Res, December 1, 2006; 72(3): 384 - 393. [Abstract] [Full Text] [PDF]