Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D

Carlos Botas, Francis R Poulain, Jennifer Akiyama, Cindy Brown, Lennell Allen, Jon Goerke, John Clements, Elaine Carlson, Anne Marie Gillespie, Charles Epstein, Samuel Hawgood

Research output: Contribution to journalArticle

329 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)11869-11874
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number20
DOIs
StatePublished - Sep 29 1998
Externally publishedYes

Fingerprint

Pulmonary Surfactant-Associated Protein D
Alveolar Epithelial Cells
Surface-Active Agents
Homeostasis
Collectins
Pulmonary Alveoli
Null Lymphocytes
Homologous Recombination
Alveolar Macrophages
Mutant Proteins
Embryonic Stem Cells
Innate Immunity
Phospholipids
Alleles
Macrophages
Lipids

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 journalArticle

Botas, C, Poulain, FR, Akiyama, J, Brown, C, Allen, L, Goerke, J, Clements, J, Carlson, E, Gillespie, AM, Epstein, C & Hawgood, S 1998, 'Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D', Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 20, pp. 11869-11874. https://doi.org/10.1073/pnas.95.20.11869
Botas, Carlos ; Poulain, Francis R ; Akiyama, Jennifer ; Brown, Cindy ; Allen, Lennell ; Goerke, Jon ; Clements, John ; Carlson, Elaine ; Gillespie, Anne Marie ; Epstein, Charles ; Hawgood, Samuel. / Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 20. pp. 11869-11874.
@article{3973f00c08c24614801c013d5f594bd5,
title = "Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D",
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.",
author = "Carlos Botas and Poulain, {Francis R} and Jennifer Akiyama and Cindy Brown and Lennell Allen and Jon Goerke and John Clements and Elaine Carlson and Gillespie, {Anne Marie} and Charles Epstein and Samuel Hawgood",
year = "1998",
month = "9",
day = "29",
doi = "10.1073/pnas.95.20.11869",
language = "English (US)",
volume = "95",
pages = "11869--11874",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "20",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=13144282686&partnerID=8YFLogxK

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 -