Surfactant protein B inhibits endotoxin-induced lung inflammation.
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.
Epaud
Ralph
R
Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Ikegami
Machiko
M
Whitsett
Jeffrey A
JA
Jobe
Alan H
AH
Weaver
Timothy E
TE
Akinbi
Henry T
HT
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology; D006579:Heterozygote; D007249:Inflammation / Q000378:metabolism*; D008170:Lung Compliance / Q000187:drug effects; D008171:Lung Diseases / Q000378:metabolism*; D008176:Lung Volume Measurements; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011663:Pulmonary Surfactants / Q000378:metabolism*; D013500:Surface Tension / Q000187:drug effects; D014132:Trachea
D016207:Cytokines; D004731:Endotoxins; D037701:Pulmonary Surfactant-Associated Protein B; D011663:Pulmonary Surfactants