Role of the plasmin-generating system in the developing nervous tissue: I. Proteolysis as a mitogenic signal for the glial cells.

The role of the plasmin-generating system, a serum component, in the development of dissociated embryonic chick spinal cord cells in culture was studied. Studies were performed in a defined system where the cells were maintained in a serum-free medium. Under these conditions the cells produce plasminogen activator. It was found that plasminogen, when added to the chemically defined culture medium at concentrations of 0.2-0.75 microgram/ml, stimulates [3H]thymidine uptake (as expressed per total DNA) in a dose-response manner. This mitogenic effect is abolished by the protease inhibitors leupeptin and aprotinin. Trypsin, but not chymotrypsin, can produce similar effects. It is concluded that plasmin, which is produced as a result of the activation of plasminogen, is a component that serves as a proliferation factor in developing spinal cords in culture.