Plasminogen activator secretion by granule neurons in cultures of developing cerebellum.

Abstract

Dispersed cell cultures were established from 7-9 day postnatal mouse cerebellum. The fibrin slide method was used to obtain a localization of plasminogen activator production to specific cells. Fibrinolytically active cells were small (5- to 8-.mu.m diameter), round and occurred singly or in aggregates. Fibrinolysis was both plasminogen and time dependent, inihibitable by .epsilon.-aminocaproic acid and soybean trypsin inhibitor and did not occur when cells were fixed in formalin prior to the fibrin overlay. Strong fibrin degradation occurred only when granule neurons were abundant in the cultures. These plasminogen activator secreting cells were identified as granule neurons by cell separation methods, nuclear morphology and their ability to bind tetanus toxin and rabbit antiserum against mouse cerebellum (anti-Cbl-1 antiserum). Plasminogen activator could be quantified in fractionated tissue homogenates or in cell culture medium by the 125I-labeled fibrin plate assay. Fibrinolysis in cerebellar extracts was 95% dependent on the presence of added plasminogen; more, the activity was greater in cerebellar extracts compared to cerebral cortex of the same age. At the age examined, the cerebellum contains many migratory neurons, and plasminogen activator production may be involved in the process of cell movement.