HEPARIN AND PGE(2) INHIBIT DNA-SYNTHESIS IN HUMAN AIRWAY SMOOTH-MUSCLE CELLS IN CULTURE

An increase in the bulk of the airway smooth muscle is a characteristi c of asthma. Much of the research investigating the mechanisms of this increase in muscle has focused on mediators that are mitogenic for sm ooth muscle, while relatively few studies have focused on mediators in hibiting mitogenesis. In this study we have examined the effects of tw o mediators proposed as regulators of smooth muscle proliferation, nam ely heparin and prostaglandin (PG) E(2), on human airway smooth muscle cells in culture stimulated with 1, 2.5, 5, and 10% fetal bovine seru m (FBS) and platelet-derived growth factor AB (PDGF), 50 ng/ml. PGE(2) had a biphasic effect on DNA synthesis in the presence of 1% FBS, wit h 10(-6) M causing inhibition and 10(-7) M causing an increase in DNA synthesis. PGE(2) caused inhibition of DNA synthesis in the presence o f 2.5, 5, and 10% FBS. Heparin (10 and 100 U/ml) caused an inhibition of DNA synthesis induced by 1% FBS, while 100 U/ml inhibited DNA synth esis induced by 5 and 10% FBS. PGE(2) (10(-8), 10(-7), and 10(-6) M) i nhibited the DNA synthesis induced by PDGF, while heparin (1, 10, and 100 U/ml) had no effect. These results indicate that both PGE(2) and h eparin may have a role in the control of human airway smooth muscle ce ll growth.