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Correction of pulmonary abnormalities in Sftpd-/- mice requires the collagenous domain of surfactant protein D.

Authors: Kingma, PS  Zhang, L  Ikegami, M  Hartshorn, K  McCormack, FX  Whitsett, JA 
Citation: Kingma PS, etal., J Biol Chem. 2006 Aug 25;281(34):24496-505. Epub 2006 Jun 20.
Pubmed: (View Article at PubMed) PMID:16787926
DOI: Full-text: DOI:10.1074/jbc.M600651200

Surfactant protein D (SP-D) is a member of the collectin family of innate defense proteins. Members of this family share four distinct structural domains: an N-terminal cross-linking domain, a collagenous domain, a neck region, and a carbohydrate recognition domain. In this study, the function of the collagenous domain was evaluated by expressing a SP-D collagen deletion mutant protein (rSftpdCDM) in wild type and SP-D null mice (Sftpd(-/-)). rSftpdCDM formed disulfide-linked trimers that further oligomerized into higher order structures. The mutant protein effectively bound carbohydrate and aggregated bacteria in vitro. Whereas rSftpdCDM did not disrupt pulmonary morphology or surfactant phospholipid levels in wild type mice, the mutant protein failed to rescue the emphysema or enlarged foamy macrophages that are characteristic of Sftpd(-/-) mice. Moreover, rSftpdCDM partitioned with small aggregate surfactant in a manner similar to SP-D, but rSftpdCDM did not correct the abnormal surfactant ultrastructure or phospholipid levels observed in Sftpd(-/-) mice. In contrast, rSftpdCDM completely corrected viral clearance and the abnormal inflammatory response that occurs following pulmonary influenza A challenge in Sftpd(-/-) mice. Our findings indicate that the collagen domain of SP-D is not required for assembly of disulfide-stabilized oligomers or the innate immune response to viral pathogens. The collagen domain of SP-D is required for the regulation of pulmonary macrophage activation, airspace remodeling, and surfactant lipid homeostasis.

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RGD Object Information
RGD ID: 4143518
Created: 2010-09-28
Species: All species
Last Modified: 2010-09-28
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.