Cellular interactions in pulmonary oxygen toxicity in vitro: II. Hyperoxia causes adult rat lung fibroblast cultures to produce apparently autocrine growth factors.

Mixed lung cell cultures from adult rats were exposed to 21, 50, or 95% O2. In the presence of serum, actively dividing mixed lung cell cultures acutely exposed to 50% O2 had a reduced rate of cell division, while 95% O2 caused growth arrest and cell death. In the absence of serum, 95% O2 again caused cell death, while cell numbers were stable for up to 1 week in 21 or 50% O2. These cells adapted to the nonlethal 50% O2 environment by a 48% increase in superoxide dismutase activity, which was not seen with the lethal 95% O2 environment. Under serum-free conditions, conditioned medium collected from cells exposed to 50% O2, but not 21% O2, contained transferable factors that increased DNA synthesis in other nonhyperoxic mixed lung cell cultures. In a series of studies to determine both the source and target cell types for this growth factor(s), the lung fibroblast was found to release an apparently autocrine growth stimulator, with an apparent molecular weight of approximately 96,000, over the first 3 days of 50% O2 exposure. A separate apparently autocrine growth stimulator, with molecular weight approximately 7000-9000, was released over the second 3 days of a 6-day exposure to 50% O2.