| First Author | Ramadas RA | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 3 | Pages | 1560-7 |
| PubMed ID | 19155504 | Mgi Jnum | J:144324 |
| Mgi Id | MGI:3830748 | Doi | 10.4049/jimmunol.182.3.1560 |
| Citation | Ramadas RA, et al. (2009) Surfactant protein A enhances production of secretory leukoprotease inhibitor and protects it from cleavage by matrix metalloproteinases. J Immunol 182(3):1560-7 |
| abstractText | Mice lacking surfactant protein A (SP-A) are susceptible to bacterial infection associated with an excessive inflammatory response in the lung. To determine mechanisms by which SP-A is antiinflammatory in the lung during bacterial infection, SP-A regulation of secretory leukoprotease inhibitor (SLPI), an inhibitor of serine proteases, was assessed. SLPI protein expression and antineutrophil elastase activity were reduced in bronchoalveolar fluid of SP-A(-/-) compared with SP-A(+/+) mice. Intratracheal administration of SP-A to SP-A(-/-) mice enhanced SLPI protein expression and antineutrophil elastase activity in the lung. SLPI mRNA was similar in whole lung and alveolar type II cells; however, it was significantly reduced in alveolar macrophages from SP-A(-/-) compared with SP-A(+/+) mice. In vitro, SP-A enhanced SLPI production by macrophage THP-1 cells but not respiratory epithelial A549 cells. SP-A inhibited LPS induced IkappaB-alpha degradation in THP-1 cells, which was partially reversed with knockdown of SLPI. Matrix metalloproteinase (MMP)-12 cleaved SLPI and incubation with SP-A reduced MMP-12-mediated SLPI cleavage. The collagen-like region of SP-A conferred protection of SLPI against MMP mediated cleavage. SP-A plays an important role in the lung during bacterial infection regulating protease and antiprotease activity. |
