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Am J Physiol Lung Cell Mol Physiol 279: L950-L957, 2000;
1040-0605/00 $5.00
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Vol. 279, Issue 5, L950-L957, November 2000

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

Luis Vázquez de Lara1, Carina Becerril2, Martha Montaño2, Carlos Ramos2, Vilma Maldonado3, Jorge Meléndez3, David S. Phelps4, Annie Pardo5, and Moisés Selman2

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


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