Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Surfactant protein B (SP-B) is a 79-amino acid hydrophobic surfactant protein that plays a critical role in postnatal lung function. Homozygous SP-B (-/-)-deficient mice die of respiratory failure at birth, associated with severe pulmonary dysfunction and atelectasis. Heterozygous SP-B (+/-)-deficient mice have 50% less SP-B protein, proprotein, and SP-B mRNA compared with control mice and are highly susceptible to oxygen-induced lung injury. In the current study, we tested whether the susceptibility of SP-B (+/-) mice to hyperoxia was restored by intratracheal administration of exogenous SP-B. After exposure to 95% oxygen for 3 d, opening pressures were increased and maximal lung volumes were significantly decreased in SP-B (+/-) mice compared with SP-B (+/+) mice. SP-B (+/-) mice were administered purified bovine SP-B (2%) with DL-alpha dipalmitoyl phosphatidylcholine (DPPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-( -glycerol)] (POPG) phospholipids or DPPC and POPG phospholipids intratracheally and exposed to 95% oxygen. SP-B-treated SP-B (+/-) mice survived longer in 95% oxygen. Although decreased lung function in SP-B (+/-) mice exposed to oxygen was not altered by administration of DPPC and POPG, administration of lipids containing 2% purified bovine SP-B restored lung function when assessed after 3 d in oxygen. Abnormalities in pulmonary function in SP-B (+/-) mice after oxygen exposure were associated with increased alveolar capillary leak, which was corrected by administration of SP-B with DPPC and POPG. Likewise, histologic abnormalities caused by oxygen-induced lung injury were improved by administration of SP-B with DPPC and POPG. Administration of phospholipids with the active SP-B peptide was sufficient to restore pulmonary function and prevent alveolar capillary leak after oxygen exposure, demonstrating the protective role of SP-B during oxygen-induced lung injury.
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PMID:Surfactant protein B corrects oxygen-induced pulmonary dysfunction in heterozygous surfactant protein B-deficient mice. 1059 28

Surfactant protein B (SP-B) is known to promote surfactant phospholipid film formation and reduce surface tension. Native SP-B is a homodimer in which subunit association is stabilized via covalent linkage through cysteine 48. We hypothesized that loss of the intersubunit bridge would alter SP-B function and lead to increased inflammation in response to challenge by hyperoxia or endotoxin. Transgenic mice in which SP-B cysteine 48 was mutated to serine were generated and crossed into the SP-B(-/-) background. Wild-type mice and transgenic mice carrying a single copy (SP-Bmon(+)) or two copies (SP-Bmon(++)) of the transgene were exposed to 95% O2 for 3 days or intratracheally injected with 10 microg of endotoxin. Interleukin-1beta, major intrinsic protein 2, and interleukin-6 in lung homogenates after 3 days of hyperoxia were significantly higher (P < 0.001) in SP-Bmon(+) mice than SP-Bmon(++) or wild-type mice. At 16 h after endotoxin injection, cytokines in lung tissues were higher in SP-Bmon(+) mice compared with wild-type mice (P < 0.05). Consistent with prolonged recovery in SP-Bmon(+) mice, the percentage of apoptotic cells in alveolar lavage was significantly lower in SP-Bmon(+) mice than in SP-Bmon(++) and wild-type mice. Overall, increased inflammation in SP-Bmon(+) mice was corrected to a large extent by increased gene dosage, indicating that formation of the intersubunit disulfide bridge is not critical for SP-B function.
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PMID:Intersubunit disulfide bridge is not required for the protective role of SP-B against lung inflammation. 1213 57