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Am J Physiol Lung Cell Mol Physiol 277: L401-L411, 1999;
1040-0605/99 $5.00
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Vol. 277, Issue 2, L401-L411, August 1999

Syntaxin 1A is transiently expressed in fetal lung mesenchymal cells: potential developmental roles

Bradley B. Brimhall1, Kristan A. Sikorski1, John Torday2, Aliakbar Shahsafaei1, Kathleen J. Haley3, and Mary E. Sunday1

1 Department of Pathology, Children's Hospital, Brigham and Women's Hospital, and Harvard Medical School, and 3 Division of Pulmonary-Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; and 2 Division of Neonatology, Department of Pediatrics, Harbor-University of California, Los Angeles Medical Center, Torrance, California 90502

Lung development is a complex process in which epithelial-mesenchymal interactions play a key role. A conserved secretory apparatus, the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, is essential for exocytosis in many cell types. Syntaxins, located on the terminal plasma membrane (T-SNAREs), are a critical component of the secretosomal complex involved in vesicular docking, fusion, and exocytosis. We analyzed syntaxin 1A mRNA and protein in fetal rat lung ontogeny, demonstrating peak expression on about day 19 of embryonic development, immediately preceding type II pneumocyte differentiation. Syntaxin 1A is predominantly expressed by lipofibroblasts, which are required for bombesin-like peptide-induced surfactant phospholipid synthesis (choline uptake) by isolated type II cells. In organ cultures, anti-syntaxin 1A antibody HPC-1 blocks choline uptake both at baseline and when induced by bombesin-like peptide or dexamethasone. HPC-1 also promotes thymidine uptake in parallel in a dose-dependent fashion. These observations indicate a potential role for syntaxin 1A during fetal lung development, possibly through involvement in secretion of mesenchymal cell-derived factors that induce terminal type II cell differentiation.

lung development; bombesin; dexamethasone; monoclonal antibody; surfactant phospholipids


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