| First Author | Ikegami M | Year | 2002 |
| Journal | J Appl Physiol (1985) | Volume | 93 |
| Issue | 2 | Pages | 505-11 |
| PubMed ID | 12133857 | Mgi Jnum | J:134699 |
| Mgi Id | MGI:3789543 | Doi | 10.1152/japplphysiol.01137.2001 |
| Citation | Ikegami M, et al. (2002) Intersubunit disulfide bridge is not required for the protective role of SP-B against lung inflammation. J Appl Physiol 93(2):505-11 |
| abstractText | 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. |
