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American Journal of Respiratory Cell and Molecular Biology. Vol. 28, pp. 373-378, 2003
© 2003 American Thoracic Society
DOI: 10.1165/rcmb.2002-0071OC

Surfactant Protein B Inhibits Endotoxin-Induced Lung Inflammation

Ralph Epaud, Machiko Ikegami, Jeffrey A. Whitsett, Alan H. Jobe, Timothy E. Weaver and Henry T. Akinbi

Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

Address correspondence to: Henry T. Akinbi, M.D., Cincinnati Children's Hospital Medical Center, Division of Pulmonary Biology, 3333 Burnet Avenue, Cincinnati, OH 45229-3039. E-mail: henry.akinbi{at}chmcc.org

Transgenic mice, in which the level of surfactant protein (SP)-B mature peptide varied 5.6-fold between SP-B(+/-) and SP-B–overexpressing lines (SP-B+/+/+), were used to test the hypothesis that SP-B protects against endotoxin-induced lung inflammation. Intratracheal administration of endotoxin resulted in significantly lower concentration of SP-B mature peptide and elevated levels of total protein in bronchoalveolar lavage fluid of SP-B(+/-) mice compared with SP-B–overexpressing mice, indicating that endotoxin treatment leads to impairment of SP-B expression coincident with increased lung injury in SP-B(+/-) mice. Recruitment of inflammatory cells and elaboration of proinflammatory cytokines in bronchoalveolar lavage fluid were reduced in SP-B–overexpressing mice compared with SP-B(+/-) mice, suggesting that SP-B inhibited endotoxin-induced lung inflammation. Lung compliance and tissue damping were significantly decreased in SP-B(+/+) and SP-B(+/-) mice, but were not changed in SP-B(+/+/+) mice, consistent with a protective effect of SP-B. The minimum surface tension of large aggregate surfactant was significantly lower for surfactant isolated from SP-B–overexpressing mice, both in the absence and the presence of added plasma proteins. These data suggest that SP-B protected against endotoxin-induced lung inflammation by enhancing surfactant function, resulting in reduced lung injury, decreased influx of inflammatory cells, and lower cytokine levels; in contrast, levels of SP-B in SP-B(+/-) mice were further decreased by endotoxin treatment, likely exacerbating lung injury in this group.

Abbreviations: bronchoalveolar lavage fluid, BALF • enzyme-linked immunosorbent assay, ELISA • interleukin, IL • phosphate-buffered saline, PBS • surfactant protein, SP • tumor necrosis factor, TNF




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