1 Airway remodelling occurs in asthma and involves an increase in airway smooth muscle mass through cell proliferation and hypertrophy. Increased eosinophil density in the airways is a feature of asthma. Eosinophils exhibiting activation in the airways of asthmatics also exhibit increased expression of transforming growth factor beta (TGF-b1). We have examined the capacity of TGF-b1 and epidermal growth factor (EGF) to in¯uence airway smooth muscle division and the e ect of heparin on TGF-b1, EGF and serum-induced smooth muscle DNA synthesis in con¯uent airway smooth muscle cells (ASMC) as an indication of entry into S phase preceding mitogenesis. 2 ASMC were obtained from cell populations growing out from explanted bovine trachealis muscle sections. Cell division was monitored in sparse plated cells by direct cell counting following nuclear staining. Cell DNA synthesis in con¯uent cells was monitored by uptake of [ 3 H]-thymidine. 3 TGF-b1 (100 pM) inhibited FBS (10%)-induced smooth muscle division in sparsely plated cells (40%). TGF-b1 (100 pM) increased cell DNA synthesis (200%) in con¯uent cells in the presence of bovine serum albumin (BSA, 0.25%). EGF (0.7 nM) also increased airway smooth muscle DNA synthesis (69%) in the presence of BSA (0.25%). The facilitatory e ect of TGF-b1 was observed between 1 ± 100 pM, while that of EGF was observed between 20 ± 200 pM. 4 Heparin inhibited serum and TGF-b1-induced DNA synthesis in con¯uent ASMC (55%), consistent with our previous observation of inhibition of division in sparsely populated ASMC (Kilfeather et al., 1995a). This action of heparin was observed between concentrations of 1 ± 100 mg ml 71 . Heparin did not inhibit DNA synthesis in response to EGF. An anti-mitogenic e ect of heparin was also observed against responses to combined exposure to TGF-b1 and EGF. 5 There was a clear inhibitory e ect of heparin in absolute terms against serum-induced division in cells plated at 10, 20 and 45610 3 cells cm 72 . The inhibitory e ect of heparin was also observed at a plating density of 45,000 cells cm 72 when responses to serum were expressed as fold-stimulation of basal DNA synthesis. 6 These ®ndings demonstrate a potential role of TGF-b1, EGF and heparin-related molecules in regulation of airway smooth muscle division.
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