PULMONARY FIBROBLAST FUNCTION IN AN ACUTE LUNG INJURY MODEL

The role of pulmonary fibroblasts (PFBs) in early adult respiratory di stress syndrome is poorly understood, To investigate PFB cellular func tion in acute lung injury, New Zealand rabbits (2 to 3 kg) were given either three daily doses of phorbol myristate acetate (PMA; 65 mu g/kg , IV), a potent stimulator of oxygen radical formation, or saline (con trol), On day 4, the lungs were harvested, subjected to enzymatic dige stion, and PFBs isolated via serial subculture, Proliferation was asse ssed via 6-hour pulsed [H-3]thymidine incorporation and by creating 5- day growth curves. Confluent PFB cultures were assessed for collagen p roduction and total protein production, as well as interleukin (IL)-1 alpha secretion, Qualitative comparisons using transmission electron m icrography were also made, There were no differences between PFBs harv ested from control versus PMA-treated animals in terms of growth rates , total protein, and IL-1 alpha production. However, there was a signi ficant difference in collagen production, with the PMA-treated animals ' PFBs producing 35% more collagen than controls, Transmission electro n micrography revealed PMA fibroblasts to be smaller (two to three tim es), have more dark staining granules, and have hypertrophied smooth e ndoplasmic reticulum-all consistent with increased metabolic activity, This suggests that pulmonary fibrosis, a late development in adult re spiratory distress syndrome, may be triggered during the acute phase o f lung injury, The increase in collagen synthesis is not related to PF B proliferation or the secretion of IL-1 alpha.