Production of a growth factor(s) by fibroblasts from the lungs of ventilated premature baboons and oxygen-exposed adult hamsters

Among the pathologic findings in infants succumbing to bronchopulmonary dysplasia are peribronchiolar and alveolar fibrosis. We examined the possibility that endogenously produced growth factors might contribute to these fibrotic changes through stimulation of fibroblast replication, with a resulting increase in collagen synthesis. We cultured fibroblasts from the lungs of prematurely delivered baboons and adult hamsters exposed to 100% oxygen and tested the media from these cells to see if they produced a factor(s) that was mitogenic to normal fibroblasts. We found that lung fibroblasts from baboons delivered prematurely at 140 days of gestation and ventilated for 6 days with 100% oxygen produced a factor(s) that supported fibroblast growth. A similar factor was also secreted by fibroblasts from normal term newborn baboon lungs and from the lungs of adult hamsters exposed to 100% oxygen for 4 to 8 days. Growth factor was not secreted by lung fibroblasts from 140-day non-breathing or 24-h-ventilated premature baboons, adult baboons, or hamsters not exposed to oxygen. The growth-promoting substance is apparently a progression factor that is heat labile and inactivated by exposure to trypsin. These findings indicate that exposure of both the premature and adult lung to high concentrations of oxygen causes the elaboration of a growth factor that may induce fibroblast hyperplasia. This action may result in an increased production of connective tissue proteins and thereby contribute to the development of the fibrosis seen in bronchopulmonary dysplasia.