Mitogenic stimulation of primary cultures of lung epithelial cells by linoleic acid

The role of linoleic acid (18:2 n-6) in stimulating proliferation of normal lung epithelial cells in vitro is investigated. When 18:2 n-6 is present with insulin (I) and cholera toxin (CT), growth is stimulated synergistically. In the presence of indomethacin (10 mu M), an inhibition of proliferation is observed in I,CT, and 18:2 n-6, which can be reversed by the addition of exogenous prostaglandin E(2) (PGE(2)). Incorporation of [(14)C]18:2 n-6 with lipid-independent I, CT, and cortisol and lipid-dependent I, CT, and 18:2 n-6 conditions suggests differences in mobilization of 18:2 n-6 from the phospholipid (PL) fractions between 2 and 8 days. The decline of [(14)C]18:2 n-6 in PL fractions with lipid-dependent condition suggests that free 18:2 n-6 may be available for metabolism by the cyclooxygenase pathway. In non-proliferative cultures, an accumulation of the label in the PL fraction is observed. Proliferation in lipid-dependent conditions appears to be due to the mobilization of 18:2 n-6 whereas proliferation in lipid-independent conditions appears to be independently controlled.