Antisense inhibition of surfactant protein A decreases tubular myelin formation in human fetal lung in vitro

Jonathan M Klein; Troy A McCarthy; John M Dagle; Jeanne M Snyder

doi:10.1152/ajplung.00410.2000

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Antisense inhibition of surfactant protein A decreases tubular myelin formation in human fetal lung in vitro

Journal article

Peer reviewed

Antisense inhibition of surfactant protein A decreases tubular myelin formation in human fetal lung in vitro

Jonathan M Klein, Troy A McCarthy, John M Dagle and Jeanne M Snyder

American journal of physiology. Lung cellular and molecular physiology, Vol.282(3), pp.L386-393

03/2002

DOI: 10.1152/ajplung.00410.2000

PMID: 11839531

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Abstract

Surfactant protein A (SP-A) is the most abundant of the surfactant-associated proteins. SP-A is involved in the formation of tubular myelin, the modulation of the surface tension-reducing properties of surfactant phospholipids, the metabolism of surfactant phospholipids, and local pulmonary host defense. We hypothesized that elimination of SP-A would alter the regulation of SP-B gene expression and the formation of tubular myelin. Midtrimester human fetal lung explants were cultured for 3-5 days in the presence or absence of an antisense 18-mer phosphorothioate oligonucleotide (ON) complementary to SP-A mRNA. After 3 days in culture, SP-A mRNA was undetectable in antisense ON-treated explants. After 5 days in culture, levels of SP-A protein were also decreased by antisense treatment. SP-B mRNA levels were not affected by the antisense SP-A ON treatment. However, there was decreased tubular myelin formation in the antisense SP-A ON-treated tissue. We conclude that selective elimination of SP-A mRNA and protein results in a decrease in tubular myelin formation in human fetal lung without affecting SP-B mRNA. We speculate that SP-A is critical to the formation of tubular myelin during human lung development and that the regulation of SP-B gene expression is independent of SP-A gene expression.

Immunohistochemistry

L-Lactate Dehydrogenase - metabolism

Oligonucleotides, Antisense - pharmacology

Proteolipids - genetics

Cation Exchange Resins - pharmacology

Humans

Proteolipids - metabolism

Fetus - metabolism

Homeostasis

Pulmonary Surfactants - metabolism

RNA, Messenger - metabolism

Myelin Sheath - metabolism

Pulmonary Surfactants - genetics

Lipids - pharmacology

Pulmonary Surfactant-Associated Proteins

Proteolipids - antagonists & inhibitors

Embryonic and Fetal Development - drug effects

Pulmonary Surfactant-Associated Protein A

Lung - embryology

Pulmonary Surfactants - antagonists & inhibitors

In Vitro Techniques

Details

Title: Subtitle: Antisense inhibition of surfactant protein A decreases tubular myelin formation in human fetal lung in vitro
Creators: Jonathan M Klein - Departments of Pediatrics, University of Iowa, Iowa City, Iowa 52242-1083, USA. jonathan-klein@uiowa.edu
Troy A McCarthy
John M Dagle
Jeanne M Snyder
Resource Type: Journal article
Publication Details: American journal of physiology. Lung cellular and molecular physiology, Vol.282(3), pp.L386-393
DOI: 10.1152/ajplung.00410.2000
PMID: 11839531
NLM abbreviation: Am J Physiol Lung Cell Mol Physiol
ISSN: 1040-0605
eISSN: 1522-1504
Publisher: American Physiological Society; United States
Grant note: HL-52055 / NHLBI NIH HHS HL-50050 / NHLBI NIH HHS
Language: English
Date published: 03/2002
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Biochemistry and Molecular Biology; Neonatology
Record Identifier: 9984025284502771

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