title: A method for generating pulmonary neutrophilia using aerosolized lipopolysaccharide.
abstract: Acute lung injury (ALI) is a severe disease characterized by alveolar neutrophilia, with limited treatment options and high mortality. Experimental models of ALI are key in enhancing our understanding of disease pathogenesis. Lipopolysaccharide (LPS) derived from gram positive bacteria induces neutrophilic inflammation in the airways and lung parenchyma of mice. Efficient pulmonary delivery of compounds such as LPS is, however, difficult to achieve. In the approach described here, pulmonary delivery in mice is achieved by challenge to aerosolized Pseudomonas aeruginosa LPS. Dissolved LPS was aerosolized by a nebulizer connected to compressed air. Mice were exposed to a continuous flow of LPS aerosol in a Plexiglas box for 10 min, followed by 2 min conditioning after the aerosol was discontinued. Tracheal intubation and subsequent bronchoalveolar lavage, followed by formalin perfusion was next performed, which allows for characterization of the sterile pulmonary inflammation. Aerosolized LPS generates a pulmonary inflammation characterized by alveolar neutrophilia, detected in bronchoalveolar lavage and by histological assessment. This technique can be set up at a small cost with few appliances, and requires minimal training and expertise. The exposure system can thus be routinely performed at any laboratory, with the potential to enhance our understanding of lung pathology.
authors.affiliation: Department of Medicine, Solna and CMM, Respiratory Medicine Unit, Karolinska Institutet; abraham.roos@ki.se.
authors.forename: Abraham B
authors.initials: AB
authors.lastname: Roos
authors.affiliation: Department of Medicine, Solna and CMM, Respiratory Medicine Unit, Karolinska Institutet.
authors.forename: Tove
authors.initials: T
authors.lastname: Berg
authors.affiliation: Department of Medicine, Solna and CMM, Respiratory Medicine Unit, Karolinska Institutet.
authors.forename: Kerstin M
authors.initials: KM
authors.lastname: Ahlgren
authors.affiliation: Department of Medicine, Solna and CMM, Respiratory Medicine Unit, Karolinska Institutet.
authors.forename: Johan
authors.initials: J
authors.lastname: Grunewald
authors.affiliation: Department of Medicine, Solna and CMM, Respiratory Medicine Unit, Karolinska Institutet; Safety Science, Global Regulator Affairs & Patient Safety, AstraZeneca Global Medicines Development.
authors.forename: Magnus
authors.initials: M
authors.lastname: Nord
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology* / Q000382:microbiology*; D000336:Aerosols; D000818:Animals; D018893:Bronchoalveolar Lavage; D004195:Disease Models, Animal; D007249:Inflammation / Q000276:immunology; D007442:Intubation, Intratracheal; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*
chemical_list: D000336:Aerosols; D008070:Lipopolysaccharides