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: 291/6/L1191    most recent 00055.2006v1 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 ISI 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 ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Frank, J. A. Articles by Matthay, M. A. Search for Related Content PubMed PubMed Citation Articles by Frank, J. A. Articles by Matthay, M. A.

Alveolar macrophages contribute to alveolar barrier dysfunction in ventilator-induced lung injury

University of California, San Francisco, Departments of ¹Medicine and ²Anesthesia; ³Cardiovascular Research Institute; ⁴Northern California Institute for Research and Education; ⁵San Francisco Veterans Affairs Medical Center, San Francisco, California; and ⁶The Paul Scherrer Institute, Villigen, Switzerland

Submitted 13 February 2006 ; accepted in final form 18 July 2006

In patients requiring mechanical ventilation for acute lung injury or acute respiratory distress syndrome (ARDS), tidal volume reduction decreases mortality, but the mechanisms of the protective effect have not been fully explored. To test the hypothesis that alveolar macrophage activation is an early and critical event in the initiation of ventilator-induced lung injury (VILI), rats were ventilated with high tidal volume (HV_T) for 10 min to 4 h. Alveolar macrophage counts in bronchoalveolar lavage (BAL) fluid decreased 45% by 20 min of HV_T (P < 0.05) consistent with activation-associated adhesion. Depletion of alveolar macrophages in vivo with liposomal clodronate significantly decreased permeability and pulmonary edema following 4 h of HV_T (P < 0.05). BAL fluid from rats exposed to 20 min of HV_T increased nitric oxide synthase activity nearly threefold in naïve primary alveolar macrophages (P < 0.05) indicating that soluble factors present in the air spaces contribute to macrophage activation in VILI. Media from cocultures of alveolar epithelial cell monolayers and alveolar macrophages exposed to 30 min of stretch in vitro also significantly increased nitrite production in naïve macrophages (P < 0.05), but media from stretched alveolar epithelial cells or primary alveolar macrophages alone did not, suggesting alveolar epithelial cell-macrophage interaction was required for the subsequent macrophage activation observed. These data demonstrate that injurious mechanical ventilation rapidly activates alveolar macrophages and that alveolar macrophages play an important role in the initial pathogenesis of VILI.

alveolar epithelial barrier function; ventilator-associated lung injury; acute lung injury; acute respiratory distress syndrome

This article has been cited by other articles:

				P. R. Pedreira, E. Garcia-Prieto, D. Parra, A. Astudillo, E. Diaz, F. Taboada, and G. M. Albaiceta Effects of melatonin in an experimental model of ventilator-induced lung injury Am J Physiol Lung Cell Mol Physiol, November 1, 2008; 295(5): L820 - L827. [Abstract] [Full Text] [PDF]

				R. A. Bem, A. W. Farnand, V. Wong, A. Koski, M. E. Rosenfeld, N. van Rooijen, C. W. Frevert, T. R. Martin, and G. Matute-Bello Depletion of resident alveolar macrophages does not prevent Fas-mediated lung injury in mice Am J Physiol Lung Cell Mol Physiol, August 1, 2008; 295(2): L314 - L325. [Abstract] [Full Text] [PDF]

				A. A. Maruscak, D. W. Vockeroth, B. Girardi, T. Sheikh, F. Possmayer, J. F. Lewis, and R. A. W. Veldhuizen Alterations to surfactant precede physiological deterioration during high tidal volume ventilation Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L974 - L983. [Abstract] [Full Text] [PDF]

				C. Yamashita, A. Forbes, J. M. Tessolini, L.-J. Yao, J. F. Lewis, and R. A. W. Veldhuizen Protective effects of elevated endogenous surfactant pools to injurious mechanical ventilation Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L724 - L732. [Abstract] [Full Text] [PDF]

				R. A. Oeckler and R. D. Hubmayr Ventilator-associated lung injury: a search for better therapeutic targets Eur. Respir. J., December 1, 2007; 30(6): 1216 - 1226. [Abstract] [Full Text] [PDF]

				A. Forbes, M. Pickell, M. Foroughian, L.-J. Yao, J. Lewis, and R. Veldhuizen Alveolar macrophage depletion is associated with increased surfactant pool sizes in adult rats J Appl Physiol, August 1, 2007; 103(2): 637 - 645. [Abstract] [Full Text] [PDF]

				N. de Prost, D. Dreyfuss, and G. Saumon Evaluation of two-way protein fluxes across the alveolo-capillary membrane by scintigraphy in rats: effect of lung inflation J Appl Physiol, February 1, 2007; 102(2): 794 - 802. [Abstract] [Full Text] [PDF]