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Mechanisms responsible for surfactant changes in sepsis-induced lung injury

Dept of Physiology, Pharmacology and Medicine, Lawson Health Research Institute, the University of Western Ontario, London, Ontario, Canada.

CORRESPONDENCE: J. F. Lewis, Dept of Physiology, Pharmacology and Medicine, Lawson Health Research Institute, University of Western Ontario, London, ON N6A 4V2, Canada. Fax: 1 5196466064. E-mail: jflewis{at}uwo.ca

Keywords: Lung injury, sepsis, surfactant

Received: July 22, 2005
Accepted August 15, 2005

Pulmonary surfactant is altered in sepsis, and these changes contribute to the predisposition of septic lungs to subsequent insults, ultimately leading to acute lung injury. Specifically, the total amount of surfactant is lower in sepsis, mainly due to decreased small aggregate (SA) surfactant pools. The amount of large aggregate (LA) surfactant is not altered.

To evaluate the mechanisms responsible for these alterations, trace doses of tritium-labelled dipalmitoylphosphatidylcholine (³H-DPPC)-labelled LA were instilled intratracheally into adult rats 20 hrs after caecal ligation and perforation (CLP) or sham surgery. Animals were sacrificed at 0, 1 and 4 h after instillation and recovery of ³H-DPPC in alveolar macrophages (AM), LA and SA was measured. In separate in vitro experiments, AM isolated from CLP/sham rats were incubated with LA or SA isolated from normal animals to evaluate the uptake of these aggregates into the AM.

Results showed increased surfactant radioactivity associated with AM of CLP animals compared with sham animals both in vivo and in vitro. In addition, more ³H-DPPC label remained in LA forms in the CLP animals in vivo compared with sham.

These findings indicate that differences in surfactant aggregate uptake and large aggregate conversion occur in septic lungs, resulting in changes in surfactant pools.

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				E. L. Martin, T. A. Sheikh, K. J. Leco, J. F. Lewis, and R. A. W. Veldhuizen Contribution of alveolar macrophages to the response of the TIMP-3 null lung during a septic insult Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L779 - L789. [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]