Surfactant components modulate fibroblast apoptosis and type I collagen and collagenase-1 expression

• Published in: American journal of physiology. Lung cellular and molecular physiology 2000-11, Vol.279 (5), p.950-L957
• Main Authors: de Lara, Luis Vazquez, Becerril, Carina, Montano, Martha, Ramos, Carlos, Maldonado, Vilma, Melendez, Jorge, Phelps, David S, Pardo, Annie, Selman, Moises
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Apoptosis - physiology; Biological Products; Cell Division - drug effects; Cell Nucleus - drug effects; Cell Nucleus - ultrastructure; Cells, Cultured; Collagen - genetics; DNA Fragmentation; Fibroblasts - drug effects; Fibroblasts - physiology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Humans; Lung - cytology; Lung - drug effects; Lung - physiology; Matrix Metalloproteinase 1 - genetics; Proto-Oncogene Proteins - pharmacology; Pulmonary Surfactants - pharmacology; Tissue Inhibitor of Metalloproteinase-1 - genetics; Trans-Activators - pharmacology; Transcription, Genetic - drug effects
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.2000.279.5.l950

1  Universidad Autónoma de Puebla, Puebla, Puebla CP 72190; 2  Instituto Nacional de Enfermedades Respiratorias, México DF, CP 14080; 3  Instituto Nacional de Cancerología, México DF, CP 14000; 5  Facultad de Ciencias, Universidad Nacional Autónoma de Mexico, México DF, CP 04510, Mexico; and 4  Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033 During lung injury, fibroblasts migrate into the alveolar spaces where they can be exposed to pulmonary surfactant. We examined the effects of Survanta and surfactant protein A (SP-A) on fibroblast growth and apoptosis and on type I collagen, collagenase-1, and tissue inhibitor of metalloproteinase (TIMP)-1 expression. Lung fibroblasts were treated with 100, 500, and 1,000 µg/ml of Survanta; 10, 50, and 100 µg/ml of SP-A; and 500 µg/ml of Survanta plus 50 µg/ml of SP-A. Growth rate was evaluated by a formazan-based chromogenic assay, apoptosis was evaluated by DNA end labeling and ELISA, and collagen, collagenase-1, and TIMP-1 were evaluated by Northern blotting. Survanta provoked fibroblast apoptosis, induced collagenase-1 expression, and decreased type I collagen affecting mRNA stability ~10-fold as assessed with the use of actinomycin D. Collagen synthesis and collagenase activity paralleled the gene expression results. SP-A increased collagen expression ~2-fold and had no effect on collagenase-1, TIMP-1, or growth rate. When fibroblasts were exposed to a combination of Survanta plus SP-A, the effects of Survanta were partially reversed. These findings suggest that surfactant lipids may protect against intraluminal fibrogenesis by inducing fibroblast apoptosis and decreasing collagen accumulation. pulmonary fibrosis; surfactant protein A