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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
22
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pubmed:dateCreated |
2001-5-30
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pubmed:abstractText |
Pulmonary surfactant protein-D (SP-D) is a member of the collectin family of C-type lectins that is synthesized in many tissues including respiratory epithelial cells in the lung. SP-D is assembled predominantly as dodecamers consisting of four homotrimeric subunits each. Association of these subunits is stabilized by interchain disulfide bonds involving two conserved amino-terminal cysteine residues (Cys-15 and Cys-20). Mutant recombinant rat SP-D lacking these residues (RrSP-Dser15/20) is secreted in cell culture as trimeric subunits rather than as dodecamers. In this study, transgenic mice that express this mutant were generated to elucidate the functional importance of SP-D oligomerization in vivo. Expression of RrSP-Dser15/20 failed to correct the pulmonary phospholipid accumulation and emphysema characteristic of SP-D null (mSP-D-/-) mice. Expression of high concentrations of the mutant protein in wild-type mice reduced the abundance of disulfide cross-linked oligomers of endogenous SP-D in the bronchoalveolar lavage fluid and demonstrated a phenotype that partially overlapped with that of the SP-D-/- mice; the animals developed emphysema and foamy macrophages without the associated abnormalities in alveolar phospholipids typical of SP-D-/- mice. Development of foamy macrophages in SP-D-deficient mice is not secondary to the increased abundance of surfactant phospholipids. Disulfide cross-linked SP-D oligomers are required for the regulation of surfactant phospholipid homeostasis and the prevention of emphysema and foamy macrophages in vivo.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Disulfides,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lectins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylcholines,
http://linkedlifedata.com/resource/pubmed/chemical/Pulmonary Surfactant-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Pulmonary Surfactants,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sepharose
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
19214-9
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11278637-Animals,
pubmed-meshheading:11278637-Base Sequence,
pubmed-meshheading:11278637-Blotting, Western,
pubmed-meshheading:11278637-Bronchoalveolar Lavage Fluid,
pubmed-meshheading:11278637-Cysteine,
pubmed-meshheading:11278637-DNA, Complementary,
pubmed-meshheading:11278637-Dimerization,
pubmed-meshheading:11278637-Disulfides,
pubmed-meshheading:11278637-Dose-Response Relationship, Drug,
pubmed-meshheading:11278637-Emphysema,
pubmed-meshheading:11278637-Genotype,
pubmed-meshheading:11278637-Glycoproteins,
pubmed-meshheading:11278637-Immunoblotting,
pubmed-meshheading:11278637-Lectins,
pubmed-meshheading:11278637-Lung,
pubmed-meshheading:11278637-Macrophages,
pubmed-meshheading:11278637-Mice,
pubmed-meshheading:11278637-Mice, Transgenic,
pubmed-meshheading:11278637-Molecular Sequence Data,
pubmed-meshheading:11278637-Mutation,
pubmed-meshheading:11278637-Phenotype,
pubmed-meshheading:11278637-Phosphatidylcholines,
pubmed-meshheading:11278637-Protein Binding,
pubmed-meshheading:11278637-Protein Conformation,
pubmed-meshheading:11278637-Pulmonary Surfactant-Associated Protein D,
pubmed-meshheading:11278637-Pulmonary Surfactants,
pubmed-meshheading:11278637-Rats,
pubmed-meshheading:11278637-Recombinant Proteins,
pubmed-meshheading:11278637-Sepharose
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pubmed:year |
2001
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pubmed:articleTitle |
Activity of pulmonary surfactant protein-D (SP-D) in vivo is dependent on oligomeric structure.
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pubmed:affiliation |
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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