title: Double-hit mouse model of cigarette smoke priming for acute lung injury.
abstract: Epidemiological studies indicate that cigarette smoking (CS) increases the risk and severity of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The mechanism is not understood, at least in part because of lack of animal models that reproduce the key features of the CS priming process. In this study, using two strains of mice, we characterized a double-hit mouse model of ALI induced by CS priming of injury caused by lipopolysaccharide (LPS). C57BL/6 and AKR mice were preexposed to CS briefly (3 h) or subacutely (3 wk) before intratracheal instillation of LPS and ALI was assessed 18 h after LPS administration by measuring lung static compliance, lung edema, vascular permeability, inflammation, and alveolar apoptosis. We found that as little as 3 h of exposure to CS enhanced LPS-induced ALI in both strains of mice. Similar exacerbating effects were observed after 3 wk of preexposure to CS. However, there was a strain difference in susceptibility to CS priming for ALI, with a greater effect in AKR mice. The key features we observed suggest that 3 wk of CS preexposure of AKR mice is a reproducible, clinically relevant animal model that is useful for studying mechanisms and treatment of CS priming for a second-hit-induced ALI. Our data also support the concept that increased susceptibility to ALI/ARDS is an important adverse health consequence of CS exposure that needs to be taken into consideration when treating critically ill individuals.
authors.affiliation: Vascular Research Laboratory, Providence Veterans Affairs Medical Center/Alpert Medical School of Brown University, Providence, Rhode Island; and.
authors.forename: Pavlo
authors.initials: P
authors.lastname: Sakhatskyy
authors.affiliation: Vascular Research Laboratory, Providence Veterans Affairs Medical Center/Alpert Medical School of Brown University, Providence, Rhode Island; and.
authors.forename: Zhengke
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Vascular Research Laboratory, Providence Veterans Affairs Medical Center/Alpert Medical School of Brown University, Providence, Rhode Island; and.
authors.forename: Diana
authors.initials: D
authors.lastname: Borgas
authors.affiliation: Division of Surgical Research, Rhode Island Hospital/Alpert Medical School of Brown University, Providence, Rhode Island.
authors.forename: Joanne
authors.initials: J
authors.lastname: Lomas-Neira
authors.affiliation: Division of Surgical Research, Rhode Island Hospital/Alpert Medical School of Brown University, Providence, Rhode Island.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Surgical Research, Rhode Island Hospital/Alpert Medical School of Brown University, Providence, Rhode Island.
authors.forename: Alfred
authors.initials: A
authors.lastname: Ayala
authors.affiliation: Vascular Research Laboratory, Providence Veterans Affairs Medical Center/Alpert Medical School of Brown University, Providence, Rhode Island; and.
authors.forename: Sharon
authors.initials: S
authors.lastname: Rounds
authors.affiliation: Vascular Research Laboratory, Providence Veterans Affairs Medical Center/Alpert Medical School of Brown University, Providence, Rhode Island; and Qing_Lu@brown.edu.
authors.forename: Qing
authors.identifier: http://orcid.org/0000-0002-4088-6200
authors.initials: Q
authors.lastname: Lu
mesh_terms: D055371:Acute Lung Injury / Q000150:complications / Q000473:pathology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D004195:Disease Models, Animal; D007109:Immunity / Q000187:drug effects; D007249:Inflammation / Q000473:pathology; D008070:Lipopolysaccharides; D008168:Lung / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D012907:Smoking / Q000009:adverse effects*
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides
keywords: acute lung injury; cigarette smoke; double-hit mouse model; priming