Surfactant protein-D regulates surfactant phospholipid homeostasis in vivo

J Biol Chem. 1998 Oct 23;273(43):28438-43. doi: 10.1074/jbc.273.43.28438.

Abstract

Surfactant protein D (SP-D) is a 43-kDa member of the collectin family of collagenous lectin domain-containing proteins that is expressed in epithelial cells of the lung. The SP-D gene was targeted by homologous recombination in embryonic stem cells that were used to produce SP-D (+/-) and SP-D (-/-) mice. Both SP-D (-/-) and SP-D (+/-) mice survived normally in the perinatal and postnatal periods. Whereas no abnormalities were observed in SP-D (+/-) mice, alveolar and tissue phosphatidylcholine pool sizes were markedly increased in SP-D (-/-) mice. Increased numbers of large foamy alveolar macrophages and enlarged alveoli were also observed in SP-D (-/-) mice. Phospholipid composition was unaltered in SP-D (-/-) mice, but surfactant morphology was abnormal, consisting of dense phospholipid membranous arrays with decreased tubular myelin. The pulmonary lipoidosis in the SP-D (-/-) mice was not associated with accumulation of surfactant proteins B or C, or their mRNAs, distinguishing the disorder from alveolar proteinosis syndromes. Surfactant protein A mRNA was reduced and, SP-A protein appeared to be reduced in SP-D (-/-) compared with wild type mice. Targeting of the mouse SP-D gene caused accumulation of surfactant lipid and altered phospholipid structures, demonstrating a previously unsuspected role for SP-D in surfactant lipid homeostasis in vivo.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Female
  • Gene Expression
  • Genotype
  • Glycoproteins / deficiency
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Glycoproteins / ultrastructure
  • Heterozygote
  • Homeostasis
  • Homozygote
  • Lipidoses
  • Male
  • Mice
  • Mice, Transgenic
  • Phosphatidylcholines / metabolism*
  • Proteolipids / genetics
  • Proteolipids / metabolism
  • Pulmonary Alveoli / metabolism*
  • Pulmonary Alveoli / pathology
  • Pulmonary Surfactant-Associated Protein A
  • Pulmonary Surfactant-Associated Protein D
  • Pulmonary Surfactant-Associated Proteins
  • Pulmonary Surfactants / deficiency
  • Pulmonary Surfactants / genetics
  • Pulmonary Surfactants / metabolism*
  • Pulmonary Surfactants / ultrastructure
  • RNA, Messenger / analysis

Substances

  • Glycoproteins
  • Phosphatidylcholines
  • Proteolipids
  • Pulmonary Surfactant-Associated Protein A
  • Pulmonary Surfactant-Associated Protein D
  • Pulmonary Surfactant-Associated Proteins
  • Pulmonary Surfactants
  • RNA, Messenger