Lysosomal acid lipase over-expression disrupts lamellar body genesis and alveolar structure in the lung

Yuan Li, Yulin Qin, Huimin Li, Renliang Wu, Cong Yan, Hong Du

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The functional role of neutral lipids in the lung is poorly understood. Lysosomal acid lipase (LAL) is a critical enzyme in hydrolysis of cholesteryl esters and triglycerides to generate free fatty acids and cholesterol in lysosomes. Human LAL was over-expressed in a doxycycline-controlled system in mouse respiratory epithelial cells to accelerate intracellular neutral lipid degradation and perturb the surfactant homeostasis in the lung. In this animal system, neutral lipid concentrations of pulmonary surfactant were reduced in bronchoalveolar lavage fluid (BALF) in association with decrease of surfactant protein C (SP-C) gene expression. The size and the number of lamellar bodies in alveolar type II epithelial cells (AT II cells) were significantly reduced accordingly. The number of macrophages required for surfactant recycling in BALF was also significantly reduced. As a result of these combinatory effects, emphysema of the alveolar structure was observed. Taken together, neutral lipid homeostasis is essential for maintenance of lamellar body genesis and the alveolar structure in the lung.

Original languageEnglish
Pages (from-to)427-436
Number of pages10
JournalInternational Journal of Experimental Pathology
Volume88
Issue number6
DOIs
StatePublished - Dec 2007

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Sterol Esterase
Surface-Active Agents
Lipids
Lung
Bronchoalveolar Lavage Fluid
Homeostasis
Alveolar Epithelial Cells
Pulmonary Surfactants
Doxycycline
Cholesterol Esters
Emphysema
Recycling
Protein C
Lysosomes
Nonesterified Fatty Acids
Triglycerides
Hydrolysis
Epithelial Cells
Macrophages
Cholesterol

Keywords

  • Alveolar structure
  • Emphysema
  • Lysosomal acid lipase
  • Neutral lipids
  • Pulmonary surfactant
  • Transgenic mice

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Lysosomal acid lipase over-expression disrupts lamellar body genesis and alveolar structure in the lung. / Li, Yuan; Qin, Yulin; Li, Huimin; Wu, Renliang; Yan, Cong; Du, Hong.

In: International Journal of Experimental Pathology, Vol. 88, No. 6, 12.2007, p. 427-436.

Research output: Contribution to journalArticle

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AU - Du, Hong

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