title: Decreased surfactant protein-B expression and surfactant dysfunction in a murine model of acute lung injury.
abstract: This study examines the relationships between inflammation, surfactant protein (SP) expression, surfactant function, and lung physiology in a murine model of acute lung injury (ALI). 129/J mice received aerosolized endotoxin lipopolysaccharide [LPS] daily for up to 96 h to simulate the cytokine release and acute inflammation of ALI. Lung elastance (E(L)) and resistance, lavage fluid cell counts, cytokine levels, phospholipid and protein content, and surfactant function were measured. Lavage and lung tissue SP content were determined by Western blot and immunohistochemistry, and tissue messenger RNA (mRNA) levels were assessed by Northern blot and in situ hybridization. Tumor necrosis factor-alpha and neutrophil counts in bronchoalveolar lavage fluid increased within 2 h of LPS exposure, followed by increases in total protein, interleukin (IL)-1beta, IL-6, and interferon-gamma. E(L) increased within 24 h of LPS exposure and remained abnormal up to 96 h. SP-B protein and mRNA levels were decreased at 24, 48, and 96 h. By contrast, SP-A protein and mRNA levels and SP-C mRNA levels were not reduced. Surfactant dysfunction occurred coincident with changes in SP-B levels. This study demonstrates that lung dysfunction in mice with LPS-ALI corresponds closely with abnormal surfactant function and reduced SP-B expression.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. eingenito@partners.org
authors.forename: E P
authors.initials: EP
authors.lastname: Ingenito
authors.forename: R
authors.initials: R
authors.lastname: Mora
authors.forename: M
authors.initials: M
authors.lastname: Cullivan
authors.forename: Y
authors.initials: Y
authors.lastname: Marzan
authors.forename: K
authors.initials: K
authors.lastname: Haley
authors.forename: L
authors.initials: L
authors.lastname: Mark
authors.forename: L A
authors.initials: LA
authors.lastname: Sonna
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008171:Lung Diseases / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D011510:Proteolipids / Q000235:genetics / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D011510:Proteolipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger