| First Author | Senft AP | Year | 2005 |
| Journal | J Immunol | Volume | 174 |
| Issue | 8 | Pages | 4953-9 |
| PubMed ID | 15814723 | Mgi Jnum | J:98168 |
| Mgi Id | MGI:3577565 | Doi | 10.4049/jimmunol.174.8.4953 |
| Citation | Senft AP, et al. (2005) Surfactant protein-D regulates soluble CD14 through matrix metalloproteinase-12. J Immunol 174(8):4953-9 |
| abstractText | Surfactant protein D (SP-D) and CD14 are important innate immune defense molecules that mediate clearance of pathogens and apoptotic cells from the lung. To test whether CD14 expression and function were influenced by SP-D, the surface expression of CD14 was assessed on alveolar macrophages from SP-D-/- mice. CD14 was reduced on alveolar macrophages from SP-D-/- mice and was associated with reduced uptake of LPS and decreased production of TNF-alpha after LPS stimulation. CD14 is proteolytically cleaved from the cell surface to form a soluble peptide. Soluble CD14 (sCD14) was increased in the bronchoalveolar lavage fluid from SP-D-/- mice. Because matrix metalloproteinase (MMP)-9 and -12 activities were increased in the lungs of SP-D-/- mice, the role of these metalloproteases in the production of sCD14 was assessed. sCD14 was decreased in both MMP(9-/-)/SP-D-/- and MMP12(-/-)/SP-D-/- mice demonstrating MMP-9 and MMP-12 contribute to proteolytic shedding of CD14. The increased sCD14 seen in SP-D-/- mice was dependent upon the activation of MMP-12 via an MMP-9-dependent mechanism. Supporting this observation, MMP-12 caused the release of sCD14 from RAW 264.7 cells in vitro. In conclusion, SP-D influences innate host defense, in part, by regulating sCD14 in a process mediated by MMP-9 and MMP-12. |
