SULFATION OF EXTRACELLULAR MATRICES MODIFIES RESPONSES OF ALVEOLAR TYPE-II CELLS TO FIBROBLAST GROWTH-FACTORS

The pulmonary alveolar basement membrane (BM) associated with alveolar type II cells has been shown to be significantly less sulfated than t hat of type I cells. To examine the biological significance of this ob servation, we measured the incorporation of 5-bromodeoxyuridine (BrdU) as an indicator of DNA synthesis in isolated rat type II cells cultur ed for 72-120 h on substrata that were naturally sulfated, not sulfate d, or chemically desulfated in serum-free, hormonally defined media, w ith and without selected growth factors. The percentage of cells incor porating BrdU was significantly elevated by desulfated chondroitin sul fate in the presence of fibroblast growth factor-2 (FGF-2 or basic FGF ) and depressed by heparin in the presence of either FGF-1 or acidic F GF or FGF-2. This depressive effect was lost by removing sulfate from the heparin. Some responses were dependent on the period of time in cu lture and concentration and molecular weight of the substrata. These o bservations support the notion that sulfation per se of certain compon ents of BM is a key determinant of type II cell responses to select gr owth factors that may define patterns of proliferation and differentia tion.