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: 288/4/L599    most recent 00304.2004v1 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 (11) Citing Articles via Google Scholar Google Scholar Articles by Wilson, M. R. Articles by Takata, M. Search for Related Content PubMed PubMed Citation Articles by Wilson, M. R. Articles by Takata, M.

TRANSLATIONAL PHYSIOLOGY

EDITORIAL FOCUS

Pulmonary inflammation induced by high-stretch ventilation is mediated by tumor necrosis factor signaling in mice

Department of Anaesthetics and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom

Submitted 10 August 2004 ; accepted in final form 13 October 2004

Although high-stretch mechanical ventilation has been demonstrated to induce lung inflammation, the roles of soluble mediators, in particular TNF, remain controversial. We have previously shown in mice that high-stretch ventilation, in the absence of preceding lung injury, induces expression of bioactive TNF in lung lavage fluid early in the course of injury, but the biological significance of this, if any, has yet to be determined. We therefore investigated the pulmonary inflammatory response to a transient period of high-stretch ventilation in anesthetized mice lacking TNF receptors and mice treated with anti-TNF antibodies. A standardized stretch-induced lung injury (assessed by lung mechanics, blood gases, and lavage protein content), followed by noninjurious low-stretch ventilation for 3 h, produced significant alveolar neutrophil infiltration in wild-type mice. However, neutrophil recruitment was substantially attenuated in TNF receptor double knockout mice and in wild-type mice treated with intratracheal anti-TNF antibody. This attenuation was not associated with decreased concentrations of neutrophil attractant CXC chemokines (macrophage inflammatory protein-2 and keratinocyte-derived chemokine) in lavage fluid. In contrast to intratracheal antibody, intravenous anti-TNF antibody did not reduce neutrophil infiltration, suggesting that the role of TNF signaling is localized within the alveolar space and does not require decompartmentalization of TNF into the circulation. These findings provide the first direct evidence that pulmonary inflammation induced by high-stretch ventilation without underlying lung injury possesses a significant TNF-dependent component. The results suggest a potential for regional anti-TNF treatment in attenuating stretch-induced pulmonary inflammation.

tumor necrosis factor receptor knockout mice; anti-tumor necrosis factor antibody; chemokine; ventilator-induced lung injury

This article has been cited by other articles:

				G. R. Zosky, V. Cannizzaro, Z. Hantos, and P. D. Sly Protective mechanical ventilation does not exacerbate lung function impairment or lung inflammation following influenza A infection J Appl Physiol, November 1, 2009; 107(5): 1472 - 1478. [Abstract] [Full Text] [PDF]

				M. R. Wilson, K. P. O'Dea, D. Zhang, A. D. Shearman, N. van Rooijen, and M. Takata Role of Lung-marginated Monocytes in an In Vivo Mouse Model of Ventilator-induced Lung Injury Am. J. Respir. Crit. Care Med., May 15, 2009; 179(10): 914 - 922. [Abstract] [Full Text] [PDF]

				N. H. Hillman, T. J. M. Moss, S. G. Kallapur, C. Bachurski, J. J. Pillow, G. R. Polglase, I. Nitsos, B. W. Kramer, and A. H. Jobe Brief, Large Tidal Volume Ventilation Initiates Lung Injury and a Systemic Response in Fetal Sheep Am. J. Respir. Crit. Care Med., September 15, 2007; 176(6): 575 - 581. [Abstract] [Full Text] [PDF]

				M. R. Wilson, M. E. Goddard, K. P. O'Dea, S. Choudhury, and M. Takata Differential roles of p55 and p75 tumor necrosis factor receptors on stretch-induced pulmonary edema in mice Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L60 - L68. [Abstract] [Full Text] [PDF]

				Spoken sessions Thorax, December 1, 2005; 60(suppl_2): ii4 - ii52. [Full Text] [PDF]

				K. P. O'Dea, A. J. Young, H. Yamamoto, J. L. Robotham, F. M. Brennan, and M. Takata Lung-marginated Monocytes Modulate Pulmonary Microvascular Injury during Early Endotoxemia Am. J. Respir. Crit. Care Med., November 1, 2005; 172(9): 1119 - 1127. [Abstract] [Full Text] [PDF]

				S. Ghosh, M. R. Wilson, S. Choudhury, H. Yamamoto, M. E. Goddard, B. Falusi, N. Marczin, and M. Takata Effects of inhaled carbon monoxide on acute lung injury in mice Am J Physiol Lung Cell Mol Physiol, June 1, 2005; 288(6): L1003 - L1009. [Abstract] [Full Text] [PDF]

				L. N. Tremblay and A. S. Slutsky Pathogenesis of ventilator-induced lung injury: trials and tribulations Am J Physiol Lung Cell Mol Physiol, April 1, 2005; 288(4): L596 - L598. [Full Text] [PDF]