| Neither SP-A nor NH2-terminal domains of SP-A can substitute for SP-D in regulation of alveolar homeostasis. | |
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MedLine Citation:
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PMID: 16500946 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Surfactant proteins (SP)-A and -D are members of the collectin family of host defense proteins that share four distinct structural domains: NH(2)-terminal oligomerization, collagenous, neck, and carbohydrate recognition (CRD). To determine the specificity of the functions of these domains, the SFTPC promoter was used to express 1) full-length rat (r) Sftpa; 2) NH(2)-rSftpa/d, consisting of NH(2)-terminal and collagenous domains of SP-A with neck domain and CRD of SP-D; and 3) rSftpd/a, consisting of NH(2)-terminal and collagenous domains of SP-D with neck domain and CRD of SP-A, in Sftpd(-/-) mice. Increased expression of SP-A in Sftpd(-/-) mice did not correct the increased pulmonary saturated phosphatidylcholine levels, emphysema, or foamy alveolar macrophage and lymphocyte infiltrations characteristic of Sftpd(-/-) mice, indicating that the decreased SP-A level noted in Sftpd(-/-) mice does not account for the observed pulmonary abnormalities. The chimeric protein NH(2)-rSftpa/d was expressed and detected in the airways of transgenic mice, migrating as an SP-A-like oligomer that associated with large aggregate surfactant in a manner similar to that of SP-A rather than SP-D. NH(2)-rSftpa/d did not correct emphysema, foamy macrophage and lymphocyte infiltration, or the increased lipid accumulations characteristic of Sftpd(-/-) mice. Thus oligomerization and surfactant lipid association of SP-D requires its NH(2)-terminal and collagenous domains, which are needed for SP-D-dependent regulation of surfactant homeostasis in vivo. Attempts to express rSftpd/a fusion protein in vivo were unsuccessful. Mmp9(-/-)/Sftpd(-/-) and Mmp12(-/-)/Sftpd(-/-) mice developed air space enlargement similar to Sftpd(-/-) mice, supporting the concept that the increased expression of each metalloproteinase seen in Sftpd(-/-) lungs is not the major cause of emphysema. |
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Authors:
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Liqian Zhang; Machiko Ikegami; Thomas R Korfhagen; Francis X McCormack; Mitsuhiro Yoshida; Robert M Senior; J Michael Shipley; Steven D Shapiro; Jeffrey A Whitsett |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-02-24 |
Journal Detail:
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Title: American journal of physiology. Lung cellular and molecular physiology Volume: 291 ISSN: 1040-0605 ISO Abbreviation: Am. J. Physiol. Lung Cell Mol. Physiol. Publication Date: 2006 Aug |
Date Detail:
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Created Date: 2006-07-07 Completed Date: 2006-09-26 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: United States |
Other Details:
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Languages: eng Pagination: L181-90 Citation Subset: IM |
Affiliation:
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Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, OH 45229, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bronchoalveolar Lavage Fluid / chemistry, cytology Homeostasis* Lipids / chemistry Mice Mice, Knockout Mice, Transgenic Protein Structure, Tertiary Pulmonary Alveoli / cytology, metabolism*, pathology Pulmonary Surfactant-Associated Protein A / genetics, metabolism* Pulmonary Surfactant-Associated Protein D / genetics, metabolism* Rats Recombinant Fusion Proteins / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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HL-47328/HL/NHLBI NIH HHS; HL-56387/HL/NHLBI NIH HHS; HL-58795/HL/NHLBI NIH HHS; HL-63329/HL/NHLBI NIH HHS; HL-68861/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Lipids; 0/Pulmonary Surfactant-Associated Protein A; 0/Pulmonary Surfactant-Associated Protein D; 0/Recombinant Fusion Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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