CAPSULE AND O-ANTIGEN FROM AN EXTRAINTESTINAL ISOLATE OFESHERICHIA COLIMODULATE CYTOKINE LEVELS IN RAT MACROPHAGES IN VITRO AND IN A RAT MODEL OF PNEUMONIA
- 1 January 2007
- journal article
- research article
- Published by Taylor & Francis Ltd in Experimental Lung Research
- Vol. 33 (7), 337-356
- https://doi.org/10.1080/01902140701634819
Abstract
Gram-negative pneumonia results in significant morbidity, mortality, and cost to the healthcare system. Previously the authors demonstrated that capsule and O-antigen, virulence factors of the extraintestinal Escherichia coli isolate CP9, modulate pulmonary neutrophil influx in a rat pneumonia model. In this report, the authors utilized CP9 and mutants deficient in O-antigen (CP921), capsule (CP9.137), or both (CP923) to test the hypothesis that modulation of cytokine levels by capsule and/or O-antigen may be a contributory mechanism. Effects of capsule and O-antigen on cytokine levels in rats in vivo and in isolated pulmonary macrophages in vitro were assessed. In vivo, capsule and O-antigen had no significant effect on tumor necrosis factor (TNF)-α levels in bronchoalveolar lavage fluid (BALF), but both were associated with significant increases in the levels of interleukin (IL)-1β and Cytokine-induced neutrophil Chemoattractant-1 (CINC-1). However, potential difficulties in interpreting data occurred because challenge bacterial strains exhibited differential growth, and clearance characteristics and mixed cell populations were present. Therefore, added mechanistic studies investigated specific interactions of capsule and O-antigen with pulmonary macrophages purified from normal rats and exposed to CP9, CP921, CP9.137, or CP923 in vitro. Results indicated that the presence of capsule led to significantly increased levels of TNF-α, IL-1β, and CINC-1, whereas O-antigen significantly decreased macrophage-associated levels of these mediators. These findings support the hypothesis that CP9 capsule is proinflammatory for macrophage-induced neutrophil recruitment, whereas O-antigen attenuates macrophage production of proinflammatory mediators in pneumonia. These results expand our understanding on the mechanisms by which these virulence traits may contribute to the inflammatory pathogenesis of pneumonia.Keywords
This publication has 29 references indexed in Scilit:
- Human Neutrophil Chemotaxis Is Modulated by Capsule and O Antigen from an Extraintestinal PathogenicEscherichia coliStrainInfection and Immunity, 2003
- Outcome and attributable cost of ventilator-associated pneumonia among intensive care unit patients in a suburban medical center*Critical Care Medicine, 2003
- Ventilator-associated PneumoniaAmerican Journal of Respiratory and Critical Care Medicine, 2002
- Hospital-Acquired PneumoniaSocial psychiatry. Sozialpsychiatrie. Psychiatrie sociale, 2001
- Capsular Polysaccharide and O-Specific Antigen Divergently Modulate Pulmonary Neutrophil Influx in an Escherichia coli Model of Gram-Negative Pneumonitis in RatsInfection and Immunity, 2000
- A Comparison of Sucralfate and Ranitidine for the Prevention of Upper Gastrointestinal Bleeding in Patients Requiring Mechanical VentilationNew England Journal of Medicine, 1998
- Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventive strategies. A consensus statement, American Thoracic Society, November 1995.American Journal of Respiratory and Critical Care Medicine, 1996
- Epidemiology of Nosocomial PneumoniaSocial psychiatry. Sozialpsychiatrie. Psychiatrie sociale, 1995
- An overview of nosocomial infections, including the role of the microbiology laboratoryClinical Microbiology Reviews, 1993
- Hospital-acquired pneumonia: Overview of the current state of the art for prevention and controlEuropean Journal of Clinical Microbiology & Infectious Diseases, 1989