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Am. J. Respir. Cell Mol. Biol., Volume 25, Number 1, July, 2001 35-44

Decreased Surfactant Protein-B Expression and Surfactant Dysfunction in a Murine Model of Acute Lung Injury

Edward P. Ingenito, Rene Mora, Michael Cullivan, Yolanda Marzan, Kathleen Haley, Lena Mark, and Lawrence A. Sonna

Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Beth Israel Deaconess Medical Center, Boston; and U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts

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 (EL) 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 . EL 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.

Abbreviations: acute lung injury, ALI; acute respiratory distress syndrome, ARDS; bronchoalveolar lavage fluid, BALF; complementary DNA, cDNA; lung elastance, EL; glyceraldehyde-3-phosphate dehydrogenase, GAPDH; equilibrium surface tension, gamma equil; maximum surface tension during dynamic expansion, gamma max; minimum surface tension during dynamic compresison, gamma min; interferon, IFN; interleukin IL; kilobase pairs, kbp; large aggregate PL, LAPL; lipopolysaccharide, LPS; messenger RNA, mRNA; phosphate-buffered saline, PBS; phospholipid, PL; lung resistance, RL; sodium dodecyl sulfate, SDS; surfactant protein, SP; saline (or standard) sodium citrate, SSC; tumor necrosis factor, TNF; total protein, TP.




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Copyright © 2001 American Thoracic Society.