Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
2001-10-15
pubmed:abstractText
Pulmonary surfactant isolated from gene-targeted surfactant protein A null mice (SP-A(-/-)) is deficient in the surfactant aggregate tubular myelin and has surface tension-lowering activity that is easily inhibited by serum proteins in vitro. To further elucidate the role of SP-A and its collagen-like region in surfactant function, we used the human SP-C promoter to drive expression of rat SP-A (rSPA) or SP-A containing a deletion of the collagen-like domain (DeltaG8-P80) in the Clara cells and alveolar type II cells of SP-A(-/-) mice. The level of the SP-A in the alveolar wash of the SP-A(-/-,rSP-A) and SP-A(-/-,DeltaG8-P80) mice was 6.1-and 1.3-fold higher, respectively, than in the wild type controls. Tissue levels of saturated phosphatidylcholine were slightly reduced in the SP-A(-/-,rSP-A) mice compared with SP-A(-/-) littermates. Tubular myelin was present in the large surfactant aggregates isolated from the SP-A(-/-,rSP-A) lines but not in the SP-A(-/-,DeltaG8-P80) mice or SP-A(-/-) controls. The equilibrium and minimum surface tensions of surfactant from the SP-A(-/-,rSP-A) mice were similar to SP-A(-/-) controls, but both were markedly elevated in the SP-A(-/-,DeltaG8-P80) mice. There was no defect in the surface tension-lowering activity of surfactant from SP-A(+/+,DeltaG8-P80) mice, indicating that the inhibitory effect of DeltaG8-P80 on surface activity can be overcome by wild type levels of mouse SP-A. The surface activity of surfactant isolated from the SP-A(-/-,rSP-A) but not the SP-A(-/-,DeltaG8-P80) mice was more resistant than SP-A(-/-) littermate control animals to inhibition by serum proteins in vitro. Pressure volume relationships of lungs from the SP-A(-/-), SP-A(-/-,rSP-A), and SP-A(-/-,DeltaG8-P80) lines were very similar. These data indicate that expression of SP-A in the pulmonary epithelium of SP-A(-/-) animals restores tubular myelin formation and resistance of isolated surfactant to protein inhibition by a mechanism that is dependent on the collagen-like region.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
38542-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11504713-Animals, pubmed-meshheading:11504713-Blotting, Southern, pubmed-meshheading:11504713-Collagen, pubmed-meshheading:11504713-Gene Deletion, pubmed-meshheading:11504713-Humans, pubmed-meshheading:11504713-Immunoblotting, pubmed-meshheading:11504713-Lung, pubmed-meshheading:11504713-Mice, pubmed-meshheading:11504713-Mice, Knockout, pubmed-meshheading:11504713-Mice, Transgenic, pubmed-meshheading:11504713-Microscopy, Electron, pubmed-meshheading:11504713-Myelin Sheath, pubmed-meshheading:11504713-Phosphatidylcholines, pubmed-meshheading:11504713-Promoter Regions, Genetic, pubmed-meshheading:11504713-Protein Structure, Tertiary, pubmed-meshheading:11504713-Proteolipids, pubmed-meshheading:11504713-Pulmonary Alveoli, pubmed-meshheading:11504713-Pulmonary Surfactant-Associated Protein A, pubmed-meshheading:11504713-Pulmonary Surfactant-Associated Proteins, pubmed-meshheading:11504713-Pulmonary Surfactants, pubmed-meshheading:11504713-Rats, pubmed-meshheading:11504713-Surface Tension, pubmed-meshheading:11504713-Surface-Active Agents, pubmed-meshheading:11504713-Time Factors, pubmed-meshheading:11504713-Transgenes
pubmed:year
2001
pubmed:articleTitle
The collagen-like region of surfactant protein A (SP-A) is required for correction of surfactant structural and functional defects in the SP-A null mouse.
pubmed:affiliation
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Cincinnati School of Medicine, Cincinnati, Ohio 45229-3039, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't