Pulmonary fibroblast function in an acute lung injury model.

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