Decreased surfactant protein-B expression and surfactant dysfunction in a marine model of acute lung injury

This study examines the relationships between inflammation, surfactant prot ein (SP) expression, surfactant function, and lung physiology in a marine m odel of acute lung injury (ALI). 129/1 mice received aerosolized endotoxin lipopolysaccharide [LPS] daily for up to 96 h to simulate the cytokine rele ase and acute inflammation of ALI. Lung elastance (E-L) and resistance, lav age fluid cell counts, cytokine levels, phospholipid and protein content, a nd surfactant function were measured. Lavage and lung tissue SP content wer e determined by Western blot and immunohistochemistry, and tissue messenger RNA (mRNA) levels were assessed by Northern blot and in situ hybridization . Tumor necrosis factor-a and neutrophil counts in bronchoalveolar lavage f luid increased within 2 h of LPS exposure, followed by increases in total p rotein, interleukin (IL)-1 beta, 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 prote in and mRNA levels and SP-C mRNA levels were not reduced. Surfactant dysfun ction occurred coincident with changes in SP-B levels. This study demonstra tes that lung dysfunction in mice with LPS-ALI corresponds closely with abn ormal surfactant function and reduced SP-B expression.