Source:http://linkedlifedata.com/resource/pubmed/id/12015304
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
30
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| pubmed:dateCreated |
2002-7-22
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| pubmed:abstractText |
The N-terminal domains of the lung collectins, surfactant proteins A (SP-A) and D (SP-D), are critical for surfactant phospholipid interactions and surfactant homeostasis, respectively. To further assess the importance of lung collectin N-terminal domains in surfactant structure and function, a chimeric SP-D/SP-A (D/A) gene was constructed by substituting nucleotides encoding amino acids Asn(1)-Ala(7) of rat SP-A with the corresponding N-terminal sequences from rat SP-D, Ala(1)-Asn(25). Recombinant D/A migrated as a 35-kDa band on reducing SDS-PAGE and as a ladder of disulfide-linked multimers under nonreducing conditions. The recombinant D/A bound and aggregated phosphatidylcholine containing vesicles as effectively as rat SP-A. Mice in which endogenous pulmonary collectins were replaced with D/A were developed by human SP-C promoter-driven overexpression of the D/A gene in SP-A(-/-) and SP-D(-/-) animals. Analysis of lavage fluid from SP-A(-/-,D/A) mice revealed that glycosylated, oligomeric D/A was secreted into the air spaces at levels that were comparable with the authentic collectins and that the N-terminal interchange converted SP-A from a "bouquet" to a cruciform configuration. Transmission electron microscopy of surfactant from the SP-A(-/-,D/A) mice revealed atypical tubular myelin containing central "target-like" electron density. Surfactant isolated from SP-A(-/-,D/A) mice exhibited elevated surface tension both in the presence and absence of plasma inhibitors, but whole lung compliance of the SP-A(-/-,D/A) animals was not different from the SP-A(-/-) littermates. Lung-specific overexpression of D/A in the SPD(-/-) mouse resulted in hetero-oligomer formation with mouse SP-A and did not correct the air space dilation or phospholipidosis that occurs in the absence of SP-D. These studies indicate that the N terminus of SP-D 1) can functionally replace the N terminus of SP-A for lipid aggregation and tubular myelin formation, but not for surface tension lowering properties of SP-A, and 2) is not sufficient to reverse the structural and metabolic pulmonary defects in the SP-D(-/-) mouse.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Collectins,
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/Proteolipids,
http://linkedlifedata.com/resource/pubmed/chemical/Pulmonary Surfactant-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Pulmonary Surfactant-Associated...,
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/Surface-Active Agents
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
26
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| pubmed:volume |
277
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
26971-9
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:12015304-Animals,
pubmed-meshheading:12015304-Carrier Proteins,
pubmed-meshheading:12015304-Cell Line,
pubmed-meshheading:12015304-Chromatography, Gel,
pubmed-meshheading:12015304-Collectins,
pubmed-meshheading:12015304-DNA, Complementary,
pubmed-meshheading:12015304-Disulfides,
pubmed-meshheading:12015304-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:12015304-Glycoproteins,
pubmed-meshheading:12015304-Humans,
pubmed-meshheading:12015304-Immunoblotting,
pubmed-meshheading:12015304-Insects,
pubmed-meshheading:12015304-Lipid Metabolism,
pubmed-meshheading:12015304-Lung,
pubmed-meshheading:12015304-Mice,
pubmed-meshheading:12015304-Mice, Transgenic,
pubmed-meshheading:12015304-Microscopy, Electron,
pubmed-meshheading:12015304-Models, Genetic,
pubmed-meshheading:12015304-Myelin Sheath,
pubmed-meshheading:12015304-Promoter Regions, Genetic,
pubmed-meshheading:12015304-Protein Conformation,
pubmed-meshheading:12015304-Protein Structure, Tertiary,
pubmed-meshheading:12015304-Proteolipids,
pubmed-meshheading:12015304-Pulmonary Surfactant-Associated Protein A,
pubmed-meshheading:12015304-Pulmonary Surfactant-Associated Protein D,
pubmed-meshheading:12015304-Pulmonary Surfactant-Associated Proteins,
pubmed-meshheading:12015304-Pulmonary Surfactants,
pubmed-meshheading:12015304-Rats,
pubmed-meshheading:12015304-Recombinant Proteins,
pubmed-meshheading:12015304-Surface-Active Agents,
pubmed-meshheading:12015304-Time Factors
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| pubmed:year |
2002
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| pubmed:articleTitle |
The role of pulmonary collectin N-terminal domains in surfactant structure, function, and homeostasis in vivo.
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| pubmed:affiliation |
Division of Pulmonary/Critical Care Medicine, Department of Medicine, Children's Hospital Research Foundation, University of Cincinnati School of Medicine, Cincinnati, OH 45267-0564, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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