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) Alert me when this article is cited Alert me if a correction is posted Citation Map Services 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 Baleeiro, C. E. O. Articles by Paine, R. Search for Related Content PubMed PubMed Citation Articles by Baleeiro, C. E. O. Articles by Paine, R., III Pubmed/NCBI databases Compound via MeSH Substance via MeSH

Sublethal Hyperoxia Impairs Pulmonary Innate Immunity¹

Carlos E. O. Baleeiro^*, Steven E. Wilcoxen^*, Susan B. Morris^*, Theodore J. Standiford and Robert Paine, III^2,*

^* Division of Pulmonary and Critical Care Medicine, Department of Veterans Affairs Medical Center, University of Michigan, Ann Arbor, MI 48105; and Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI 48109

Supplemental oxygen is often required in the treatment of critically ill patients. The impact of hyperoxia on pulmonary host defense is not well-established. We hypothesized that hyperoxia directly impairs pulmonary host defense, beyond effects on alveolar wall barrier function. C57BL/6 mice were kept in an atmosphere of >95% O₂ for 4 days followed by return to room air. This exposure does not lead to mortality in mice subsequently returned to room air. Mice kept in room air served as controls. Mice were intratracheally inoculated with Klebsiella pneumoniae and followed for survival. Alveolar macrophages (AM) were harvested by bronchoalveolar lavage after 4 days of in vivo hyperoxia for ex vivo experiments. Mortality from pneumonia increased significantly in mice exposed to hyperoxia compared with infected mice in room air. Burden of organisms in the lung and dissemination of infection were increased in the hyperoxia group whereas accumulation of inflammatory cells in the lung was impaired. Hyperoxia alone had no impact on AM numbers, viability, or ability to phagocytize latex microbeads. However, following in vivo hyperoxia, AM phagocytosis and killing of Gram-negative bacteria and production of TNF- and IL-6 in response to LPS were significantly reduced. AM surface expression of Toll-like receptor-4 was significantly decreased following in vivo hyperoxia. Thus sublethal hyperoxia increases Gram-negative bacterial pneumonia mortality and has a significant adverse effect on AM host defense function. Impaired AM function due to high concentrations of supplemental oxygen may contribute to the high rate of ventilator-associated pneumonia seen in critically ill patients.

This article has been cited by other articles:

				N. M. Reddy, V. Suryanarayana, D. V. Kalvakolanu, M. Yamamoto, T. W. Kensler, P. M. Hassoun, S. R. Kleeberger, and S. P. Reddy Innate Immunity against Bacterial Infection following Hyperoxia Exposure Is Impaired in NRF2-Deficient Mice J. Immunol., October 1, 2009; 183(7): 4601 - 4608. [Abstract] [Full Text] [PDF]

				N. M. Reddy, S. R. Kleeberger, T. W. Kensler, M. Yamamoto, P. M. Hassoun, and S. P. Reddy Disruption of Nrf2 Impairs the Resolution of Hyperoxia-Induced Acute Lung Injury and Inflammation in Mice J. Immunol., June 1, 2009; 182(11): 7264 - 7271. [Abstract] [Full Text] [PDF]

				T. M. Umstead, W. M. Freeman, V. M. Chinchilli, and D. S. Phelps Age-related changes in the expression and oxidation of bronchoalveolar lavage proteins in the rat Am J Physiol Lung Cell Mol Physiol, January 1, 2009; 296(1): L14 - L29. [Abstract] [Full Text] [PDF]

				C. E. O. Baleeiro, P. J. Christensen, S. B. Morris, M. P. Mendez, S. E. Wilcoxen, and R. Paine III GM-CSF and the impaired pulmonary innate immune response following hyperoxic stress Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1246 - L1255. [Abstract] [Full Text] [PDF]

				N. G. Hall, Y. Liu, J. M. Hickman-Davis, G. C. Davis, C. Myles, E. J. Andrews, S. Matalon, and J. D. Lang Jr. Bactericidal Function of Alveolar Macrophages in Mechanically Ventilated Rabbits Am. J. Respir. Cell Mol. Biol., June 1, 2006; 34(6): 719 - 726. [Abstract] [Full Text] [PDF]

				M. P. Mendez, S. B. Morris, S. Wilcoxen, E. Greeson, B. Moore, and R. Paine III Shedding of soluble ICAM-1 into the alveolar space in murine models of acute lung injury Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L962 - L970. [Abstract] [Full Text] [PDF]

				M. A. Matthay and G. A. Zimmerman Acute Lung Injury and the Acute Respiratory Distress Syndrome: Four Decades of Inquiry into Pathogenesis and Rational Management Am. J. Respir. Cell Mol. Biol., October 1, 2005; 33(4): 319 - 327. [Full Text] [PDF]

				A. H. van Kaam, R. A. Lachmann, E. Herting, A. De Jaegere, F. van Iwaarden, L. A. Noorduyn, J. H. Kok, J. J. Haitsma, and B. Lachmann Reducing Atelectasis Attenuates Bacterial Growth and Translocation in Experimental Pneumonia Am. J. Respir. Crit. Care Med., May 1, 2004; 169(9): 1046 - 1053. [Abstract] [Full Text] [PDF]