References
Query Results -- Details
MGI Accession ID: MGI:3577565
J Number: J:98168
Other Accession IDs:
Title: Surfactant protein-D regulates soluble CD14 through matrix metalloproteinase-12.
Authors: Senft AP; Korfhagen TR; Whitsett JA; Shapiro SD; LeVine AM
Journal: J Immunol
Volume: 174
Issue: 8
Date: 2005 Apr 15
Year: 2005
Pages: 4953-9
Review Status: Peer Reviewed
Abstract:
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.
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