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

Am J Physiol Lung Cell Mol Physiol 292: L632-L643, 2007; doi:10.1152/ajplung.00326.2006
1040-0605/07 $8.00

This Article Free upon publication Full Text Full Text (PDF) 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 (1) Citing Articles via Google Scholar Google Scholar Articles by Russo, T. A. Articles by Notter, R. H. Search for Related Content PubMed PubMed Citation Articles by Russo, T. A. Articles by Notter, R. H.

Surfactant dysfunction and lung injury due to the E. coli virulence factor hemolysin in a rat pneumonia model

Departments of ¹Medicine and ²Microbiology, ³The Witebsky Center for Microbial Pathogenesis; ⁴Veterans Administration Western New York Healthcare System; Departments of ⁵Anesthesiology, ⁶Pathology, and ⁷Pediatrics, ⁸Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo; and Departments of ⁹Pediatrics, ¹⁰Environmental Medicine, and ¹¹Biomedical Engineering, University of Rochester, Rochester, New York

Submitted 24 August 2006 ; accepted in final form 27 October 2006

This study tests the hypothesis that the virulence factor hemolysin (Hly) expressed by extraintestinal pathogenic Escherichia coli contributes to surfactant dysfunction and lung injury in a rat model of gram-negative pneumonia. Rats were instilled intratracheally with CP9 (wild type, Hly-positive), CP9hlyA (Hly-minus), CP9/pEK50 (supraphysiological Hly), or purified LPS. At 6 h postinfection, rats given CP9 had a decreased percentage content of large surfactant aggregates in cell-free bronchoalveolar lavage (BAL), decreased large aggregate surface activity, decreased Pa_O2/FI_O2 ratio, increased BAL albumin/protein levels, and increased histological evidence of lung injury compared with rats given CP9hlyA or LPS. In addition, rats given CP9/pEK50 or CP9 had decreased large aggregate surface activity, decreased Pa_O2/FI_O2 ratios, and increased BAL albumin/protein levels at 2 h postinfection compared with rats given CP9hlyA. The severity of permeability lung injury based on albumin/protein levels in BAL at 2 h was ordered as CP9/pEK50 > CP9 > CP9hlyA > normal saline controls. Total lung titers of bacteria were increased at 6 h in rats given CP9 vs. CP9hlyA, but bacterial titers were not significantly different at 2 h, indicating that increased surfactant dysfunction and lung injury were associated with Hly as opposed to bacterial numbers per se. Further studies in vitro showed that CP9 could directly lyse transformed pulmonary epithelial cells (H441 cells) but that indirect lysis of H441 cells secondary to Hly-induced neutrophil lysis did not occur. Together, these data demonstrate that Hly is an important direct mediator of surfactant dysfunction and lung injury in gram-negative pneumonia.

lung surfactant dysfunction; Escherichia coli; bacterial virulence

This article has been cited by other articles:

				M. Yee, P. R. Chess, S. A. McGrath-Morrow, Z. Wang, R. Gelein, R. Zhou, D. A. Dean, R. H. Notter, and M. A. O'Reilly Neonatal oxygen adversely affects lung function in adult mice without altering surfactant composition or activity Am J Physiol Lung Cell Mol Physiol, October 1, 2009; 297(4): L641 - L649. [Abstract] [Full Text] [PDF]