MITOGENIC STIMULATION OF PRIMARY CULTURES OF LUNG EPITHELIAL-CELLS BYLINOLEIC-ACID

The role of linoleic acid (18:2 n-6) in stimulating proliferation of n ormal 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 inhibi tion 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)). Inc orporation of [C-14]18:2 n-6 with lipid-independent I, CT, and cortiso l and lipid-dependent I, CT, and 18:2 n-6 conditions suggests differen ces in mobilization of 18.2 n-6 from the phospholipid (PL) fractions b etween 2 and 8 days. The decline of [C-14]18:2 n-6 in PL fractions wit h lipid-dependent condition suggests that free 18:2 n-6 may be availab le 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 co nditions appears to be independently controlled.