title: Pulmonary contusion is associated with toll-like receptor 4 upregulation and decreased susceptibility to pseudomonas pneumonia in a mouse model.
abstract: Pulmonary contusion is a major cause of respiratory failure in trauma patients. This injury frequently leads to immune suppression and infectious complications such as pneumonia. The mechanism whereby trauma leads to an immune-suppressed state is poorly understood. To further study this phenomenon, we developed an animal model of pulmonary contusion (PC) complicated by pneumonia and assessed the effect of PC and pneumonia on toll-like receptor expression in alveolar macrophages. Using a mouse model, PC was induced on the right lung, and pneumonia was induced with Pseudomonas aeruginosa (Pa) injected intratracheally 48 h after injury. Susceptibility to pneumonia was assessed by mortality at 7 days. Uninjured animals were used as controls. Bronchoalveolar lavage fluid and blood were assayed 48 h after injury and 24 h after Pa instillation to look at markers of systemic inflammation. Toll-like receptor expression in the initial inflammatory response was analyzed by flow cytometry. Unexpectedly, injured animals subjected to intratracheal injection of Pa at 48 h after PC demonstrated increased survival compared with uninjured animals. Bronchoalveolar lavage cytokine expression was increased significantly after Pa administration but not after PC alone. Toll-like receptor 4 expression on alveolar macrophages was significantly elevated in the injured group compared with sham but not in neutrophils. Animals subjected to PC are more resistant to mortality from infection with Pa and display an enhanced cytokine response when subsequently subjected to Pa. Increased expression of toll-like receptor 4 on alveolar macrophages and enhanced innate immunity are a possible mechanism of increased cytokine production and decreased susceptibility to pneumonia.
authors.affiliation: Department Surgery, Washington University School of Medicine, St Louis, Missouri, USA. southardr@wudosis.wustl.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Southard
authors.forename: Sarbani
authors.initials: S
authors.lastname: Ghosh
authors.forename: Julia
authors.initials: J
authors.lastname: Hilliard
authors.forename: Chris
authors.initials: C
authors.lastname: Davis
authors.forename: Cristina
authors.initials: C
authors.lastname: Mazuski
authors.forename: Andrew
authors.initials: A
authors.lastname: Walton
authors.forename: Richard
authors.initials: R
authors.lastname: Hotchkiss
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004198:Disease Susceptibility; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000276:immunology; D055370:Lung Injury / Q000150:complications / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018410:Pneumonia, Bacterial / Q000150:complications / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4