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 Survant a 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 mg/ml of Survanta; 10, 50, and 100 mg/ml of SP-A; and 500 mg/ml of Survant a plus 50 mg/ml of SP-A. Growth rate was evaluated by a formazan-based chro mogenic assay, apoptosis was evaluated by DNA end labeling and ELISA, and c ollagen, collagenase-1, and TIMP-1 were evaluated by Northern blotting. Sur vanta provoked fibroblast apoptosis, induced collagenase-1 expression, and decreased type I collagen affecting mRNA stability similar to 10-fold as as sessed with the use of actinomycin D. Collagen synthesis and collagenase ac tivity paralleled the gene expression results. SP-A increased collagen expr ession similar to2-fold and had no effect on collagenase-1, TIMP-1, or grow th 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 in ducing fibroblast apoptosis and decreasing collagen accumulation.