title: Surfactant components modulate fibroblast apoptosis and type I collagen and collagenase-1 expression.
abstract: 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 microg/ml of Survanta; 10, 50, and 100 microg/ml of SP-A; and 500 microg/ml of Survanta plus 50 microg/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 approximately 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 approximately 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.
authors.affiliation: Universidad Autónoma de Puebla, Puebla, Puebla CP 72190, Mexico.
authors.forename: L
authors.initials: L
authors.lastname: Vázquez de Lara
authors.forename: C
authors.initials: C
authors.lastname: Becerril
authors.forename: M
authors.initials: M
authors.lastname: Montaño
authors.forename: C
authors.initials: C
authors.lastname: Ramos
authors.forename: V
authors.initials: V
authors.lastname: Maldonado
authors.forename: J
authors.initials: J
authors.lastname: Meléndez
authors.forename: D S
authors.initials: DS
authors.lastname: Phelps
authors.forename: A
authors.initials: A
authors.lastname: Pardo
authors.forename: M
authors.initials: M
authors.lastname: Selman
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001688:Biological Products; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics*; D053938:DNA Fragmentation; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D015534:Trans-Activators / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D001688:Biological Products; D003094:Collagen; D020781:Matrix Metalloproteinase 1; D011518:Proto-Oncogene Proteins; D011663:Pulmonary Surfactants; D019715:Tissue Inhibitor of Metalloproteinase-1; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C072197:beractant