Tumor necrosis factor-alpha decreases surfactant protein B mRNA in murine lung.
Respiratory failure secondary to acute lung inflammation is associated with quantitative and qualitative abnormalities of pulmonary surfactant. The surfactant-associated proteins (SP)-A, -B, and -C are critical for normal surfactant function, synthesis, and metabolism. Tumor necrosis factor-alpha (TNF-alpha), a primary mediator of acute lung inflammation, decreased SP gene expression in vitro (32, 34). In the present in vivo study, transient T cell activation and TNF-alpha release were initiated by intraperitoneal administration of anti-CD3 antibody 145-2C11. Serum TNF-alpha was elevated 2 h after injection of the antibody. SP-B and -C mRNA were decreased 12 and 24 h after antibody treatment. Intratracheal murine TNF-alpha also resulted in decreased SP-B and SP-C mRNA levels in the bronchiolar and alveolar epithelium of adult FVB/N mice, as demonstrated by S1 nuclease protection and in situ hybridization assays, despite minimal histological inflammation. SP-A mRNA was not significantly altered after anti-CD3 antibody and was only mildly decreased after TNF-alpha. As previously reported, intercellular adhesion molecule-1 mRNA was elevated after intratracheal TNF-alpha. SP insufficiency contributes to the pathogenesis of pulmonary diseases associated with increased TNF-alpha, such as adult respiratory distress syndrome and pneumonia (8). TNF-alpha-mediated decrease in SP gene expression may contribute to the surfactant dysfunction and atelectasis observed in inflammatory lung diseases.
Pryhuber
G S
GS
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Bachurski
C
C
Hirsch
R
R
Bacon
A
A
Whitsett
J A
JA
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D006224:Cricetinae; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D011510:Proteolipids / Q000235:genetics*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins; D014132:Trachea; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*
D000906:Antibodies; D017252:CD3 Complex; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1