Surfactant dysfunction and lung injury due to the E. coli virulence factor hemolysin in a rat pneumonia model
| Autor: | Ruth Olson, Bruce A. Holm, Janet M. Beanan, rd Paul R. Knight, Robert H. Notter, Stacy A. Genagon, Thomas A. Russo, Patricia R. Chess, Bruce A. Davidson, Zhengdong Wang |
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| Rok vydání: | 2007 |
| Předmět: |
Pulmonary and Respiratory Medicine
Physiology Neutrophils Bacterial Toxins Virulence Lung injury Biology medicine.disease_cause Bronchoalveolar Lavage Virulence factor Microbiology Hemolysin Proteins Physiology (medical) medicine Pneumonia Bacterial Animals Rats Long-Evans Escherichia coli Lung Extraintestinal Pathogenic Escherichia coli Escherichia coli Proteins Hemolysin Pulmonary Surfactants Cell Biology Lung Injury medicine.disease biology.organism_classification Enterobacteriaceae Rats Pneumonia Disease Models Animal Immunology |
| Zdroj: | American journal of physiology. Lung cellular and molecular physiology. 292(3) |
| ISSN: | 1040-0605 |
| Popis: | 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), CP9 hlyA (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 PaO2/FiO2ratio, increased BAL albumin/protein levels, and increased histological evidence of lung injury compared with rats given CP9 hlyA or LPS. In addition, rats given CP9/ pEK50 or CP9 had decreased large aggregate surface activity, decreased PaO2/FiO2ratios, and increased BAL albumin/protein levels at 2 h postinfection compared with rats given CP9 hlyA. The severity of permeability lung injury based on albumin/protein levels in BAL at 2 h was ordered as CP9 /pEK50 > CP9 > CP9 hlyA > normal saline controls. Total lung titers of bacteria were increased at 6 h in rats given CP9 vs. CP9 hlyA, 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. |
| Databáze: | OpenAIRE |
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