Surfactant components modulate fibroblast apoptosis and type I collagen and collagenase-1 expression
Por:
Vázquez De Lara L., Becerril C., Montaño M., Ramos C., Maldonado V., Meléndez J., Phelps D.S., Pardo A., Selman M.
Publicada:
1 ene 2000
Resumen:
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 ?g/ml of Survanta; 10, 50, and 100 ?g/rnl of SP-A; and 500 ?g/ml of Survanta plus 50 ?g/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 resuits. 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 intralunfinal fibrogenesis by inducing fibroblast apoptosis and decreasing collagen accumulation.
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