title: Natural protection from apoptosis by surfactant protein A in type II pneumocytes.
abstract: Surfactant-associated protein A (SP-A) is a component of pulmonary surfactant that binds to a specific receptor (SPAR) on the surface of type II alveolar cells of the lung and regulates gene expression and surfactant secretion. Previously we have shown that activation of SPAR by SP-A binding initiates a signal through pathways that involve tyrosine phosphorylation, include IRS-1, and entail activation of phosphatidylinositol 3-kinase (PI3K). In other cell types, cytokines that activate the PI3K signaling pathway promote cell survival. Therefore we investigated whether there was an effect of SP-A on apoptosis as measured by DNA laddering, FACS analysis, TUNEL assay, and annexin V binding. SP-A protected primary cultures of rat type II alveolar cells against the apoptotic effects of etoposide and UV light and also protected the H441 human Clara lung tumor cell line against staurosporine-induced apoptosis. The protective effects of SP-A were abrogated by inhibition of either tyrosine-specific protein kinase activity or PI3K. SP-A/SPAR interaction thus initiates a signaling pathway that regulates apoptosis in type II cells. These findings may be important in understanding the pathogenesis of acute lung injury and pulmonary tumorigenesis and may suggest new therapeutic options.
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, 1020 Locust Street, Philadelphia, Pennsylvania, 19107, USA. Martyn.White@mail.tju.edu
authors.forename: M K
authors.initials: MK
authors.lastname: White
authors.forename: V
authors.initials: V
authors.lastname: Baireddy
authors.forename: D S
authors.initials: DS
authors.lastname: Strayer
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D002469:Cell Separation; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011510:Proteolipids / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D006023:Glycoproteins; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D005047:Etoposide; D003907:Dexamethasone; D003513:Cycloheximide; D019869:Phosphatidylinositol 3-Kinases; D019311:Staurosporine