Surfactant components modulate fibroblast apoptosis and type I collagen and collagenase-1 expression.
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.
Vázquez de Lara
L
L
Universidad Autónoma de Puebla, Puebla, Puebla CP 72190, Mexico.
Becerril
C
C
Montaño
M
M
Ramos
C
C
Maldonado
V
V
Meléndez
J
J
Phelps
D S
DS
Pardo
A
A
Selman
M
M
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
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