SULFATION OF EXTRACELLULAR MATRICES MODIFIES GROWTH-FACTOR EFFECTS ONTYPE-II CELLS ON LAMININ SUBSTRATA

The alveolar basement membrane contains a variety of extracellular mat rix (ECM) molecules, including laminin and sulfated glycosaminoglycans of proteoglycans. These mixtures exist within microdomains of differi ng levels of sulfate, which may specifically interact to be key determ inants of the known capacity of the type II cell to respond to certain growth factors. Isolated type II cells were exposed to either acidic fibroblast growth factor (FGF-1), basic fibroblast growth factor (FGF- 2), or keratinocyte growth factor (KGF; FGF-7) on culture wells precoa ted with laminin alone or in combination with chondroitin sulfate (CS) , high-molecular-weight heparin, or their desulfated forms. Desulfated heparin significantly elevated FGF-1- and FGF-2-stimulated DNA synthe sis, whereas desulfated CS and N-desulfated heparin elevated FGF-7-sti mulated DNA synthesis by type ii cells on laminin substrata. When FGF- 1 was mixed into tl-le various test matrix substrata, DNA synthesis wa s significantly increased in all cases. These results demonstrated tha t decreased levels of sulfate in ECM substrata act to upregulate respo nses to heparin-binding growth factors by alveolar epithelial cells on laminin substrata.