Molecular mechanisms of lipopolysaccharide-caused induction of surfactant protein-A gene expression in human alveolar epithelial A549 cells

Pulmonary surfactant is a heterogeneous active surface complex made up of lipids and proteins. The major glycoprotein in surfactant is surfactant protein A (SP-A), which is released into the alveolar lumen from cytoplasmic lamellar bodies in type II alveolar epithelial cells. SP-A is involved in phospholipid absorption. SP-A together with other surfactant proteins and phospholipids prevent alveolar collapse during respiration by decreasing the surface tension of the air-liquid interface. Additionally, SP-A interacts with pathogens to prevent their propagation and regulate host immune responses. Studies in human and animal models have shown that deficiencies or mutations in surfactant components result in various lung or kidney pathologies, suggesting a role for SP-A in the development of lung and kidney diseases. In this mini-review, we discuss the current understanding of SP-A functions, recent findings of its dysfunction in specific lung and kidney pathologies, and how SP-A has been used as a biomarker to detect the outcome of lung diseases.

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

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00410.2000 ◽

2002 ◽

Vol 282 (3) ◽

pp. L386-L393 ◽

Cited By ~ 9

Author(s):

Jonathan M. Klein ◽

Troy A. McCarthy ◽

John M. Dagle ◽

Jeanne M. Snyder

Keyword(s):

Gene Expression ◽

Protein A ◽

Fetal Lung ◽

Surfactant Protein ◽

Surfactant Protein A ◽

Mrna Levels ◽

Phosphorothioate Oligonucleotide ◽

Myelin Formation ◽

Surfactant Phospholipids ◽

Human Fetal Lung

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.

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