Abstract
Surfactant protein D (SP-D) is one of two collectins found in the pulmonary alveolus. On the basis of homology with other collectins, potential functions for SP-D include roles in innate immunity and surfactant metabolism. The SP-D gene was disrupted in embryonic stem cells by homologous recombination to generate mice deficient in SP-D. Mice heterozygous for the mutant SP-D allele had SP-D concentrations that were approximately 50% wild type but no other obvious phenotypic abnormality. Mice totally deficient in SP-D were healthy to 7 months but had a progressive accumulation of surfactant lipids, SP-A, and SP-B in the alveolar space. By 8 weeks the alveolar phospholipid pool was 8-fold higher than wild-type littermates. There was also a 10-fold accumulation of alveolar macrophages in the null mice, and many macrophages were both multinucleated and foamy in appearance. Type II cells in the null mice were hyperplastic and contained giant lamellar bodies. These alterations in surfactant homeostasis were not associated with detectable changes in surfactant surface activity, postnatal respiratory function, or survival. The findings in the SP-D-deficient mice suggest a role for SP-D in surfactant homeostasis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 11869-11874 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 95 |
| Issue number | 20 |
| DOIs | |
| State | Published - Sep 29 1998 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
- General
Cite this
Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D. / Botas, Carlos; Poulain, Francis R; Akiyama, Jennifer; Brown, Cindy; Allen, Lennell; Goerke, Jon; Clements, John; Carlson, Elaine; Gillespie, Anne Marie; Epstein, Charles; Hawgood, Samuel.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 20, 29.09.1998, p. 11869-11874.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D
AU - Botas, Carlos
AU - Poulain, Francis R
AU - Akiyama, Jennifer
AU - Brown, Cindy
AU - Allen, Lennell
AU - Goerke, Jon
AU - Clements, John
AU - Carlson, Elaine
AU - Gillespie, Anne Marie
AU - Epstein, Charles
AU - Hawgood, Samuel
PY - 1998/9/29
Y1 - 1998/9/29
N2 - Surfactant protein D (SP-D) is one of two collectins found in the pulmonary alveolus. On the basis of homology with other collectins, potential functions for SP-D include roles in innate immunity and surfactant metabolism. The SP-D gene was disrupted in embryonic stem cells by homologous recombination to generate mice deficient in SP-D. Mice heterozygous for the mutant SP-D allele had SP-D concentrations that were approximately 50% wild type but no other obvious phenotypic abnormality. Mice totally deficient in SP-D were healthy to 7 months but had a progressive accumulation of surfactant lipids, SP-A, and SP-B in the alveolar space. By 8 weeks the alveolar phospholipid pool was 8-fold higher than wild-type littermates. There was also a 10-fold accumulation of alveolar macrophages in the null mice, and many macrophages were both multinucleated and foamy in appearance. Type II cells in the null mice were hyperplastic and contained giant lamellar bodies. These alterations in surfactant homeostasis were not associated with detectable changes in surfactant surface activity, postnatal respiratory function, or survival. The findings in the SP-D-deficient mice suggest a role for SP-D in surfactant homeostasis.
AB - Surfactant protein D (SP-D) is one of two collectins found in the pulmonary alveolus. On the basis of homology with other collectins, potential functions for SP-D include roles in innate immunity and surfactant metabolism. The SP-D gene was disrupted in embryonic stem cells by homologous recombination to generate mice deficient in SP-D. Mice heterozygous for the mutant SP-D allele had SP-D concentrations that were approximately 50% wild type but no other obvious phenotypic abnormality. Mice totally deficient in SP-D were healthy to 7 months but had a progressive accumulation of surfactant lipids, SP-A, and SP-B in the alveolar space. By 8 weeks the alveolar phospholipid pool was 8-fold higher than wild-type littermates. There was also a 10-fold accumulation of alveolar macrophages in the null mice, and many macrophages were both multinucleated and foamy in appearance. Type II cells in the null mice were hyperplastic and contained giant lamellar bodies. These alterations in surfactant homeostasis were not associated with detectable changes in surfactant surface activity, postnatal respiratory function, or survival. The findings in the SP-D-deficient mice suggest a role for SP-D in surfactant homeostasis.
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UR - http://www.scopus.com/inward/citedby.url?scp=13144282686&partnerID=8YFLogxK
U2 - 10.1073/pnas.95.20.11869
DO - 10.1073/pnas.95.20.11869
M3 - Article
C2 - 9751757
AN - SCOPUS:13144282686
VL - 95
SP - 11869
EP - 11874
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 20
ER -