Monolayer cultures of human epithelial and endothelial cells were used to study the association of latent transforming growth factor-1 (TGF-1) to extracellular matrices and its release and activation during matrix degradation. Human umbilical vein endothelial cells and embryonic lung fibroblasts produced relatively high levels of TGF-1, its propeptide (1-latency-associated protein), and latent TGF--binding protein and incorporated latent TGF-1 into their matrices as shown by immunoblotting. Amnion epithelial cells produced lower levels of these proteins. Confluent cultures of epithelial cells were exposed to matrix-degrading proteases and glycosidases. Mast cell chymase, leukocyte elastase, and plasmin efficiently released matrix-bound latent TGF-1 complexes, while chondroitinase ABC and heparitinases were ineffective. The ability of the proteases to activate recombinant latent TGF-1 was tested using growth inhibition assays and a novel sodium deoxycholate-polyacrylamide gel electrophoresis followed by immunoblotting. Sodium deoxycholate solubilized M 25,000 TGF-1 but did not dissociate high M latent TGF-1 complexes, allowing separation of these forms by polyacrylamide gel electrophoresis. Mast cell chymase and leukocyte elastase did not activate latent TGF-1, suggesting that its release from matrix and activation are controlled by different mechanisms. The release of TGF- from the matrix by leukocyte and mast cell enzymes may contribute to the accumulation of connective tissue in inflammation.

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