Brain plasminogen system

Endothelial cells, glial and neuronal cells, representing the principal sources of plasminogen activator (tPA and uPA), are in close interaction in the neurovascular unit. Formation of plasmin at the surface of endothelial cells and neurons has important consequences on these cells (apoptosis of endothelial cells and detachment/aggregation of neurons). The plasminogen activation system is also known to participate in various inflammatory conditions of the central nervous system. In such pathologies, beyond circulating plasminogen, the origin of plasminogen is still a matter of debate. First, we have investigated the presence of plasminogen in human cerebro-spinal fluids. The presence of plasminogen and the activity of plasmin, tPA and uPA in inflammatory diseases (GBS, Guillain Barre Syndrome patients, n = 14; MS, Multiple sclerosis, n = 9) and also in non-inflammatory diseases (n = 13) were studied. Western blotting, zymography and chromogenic detection were used to evaluate antigens and activity of plasmin(ogen), uPA and tPA. In human, plasminogen was detectable in both inflammatory (66%) and non-inflammatory (65%) patients. Plasminogen was found in larger concentration in inflammatory diseases (4.6 nM in GBS, 6.5 nM in MS and 2.2 nM in non inflammatory diseases). Active plasmin was detected in GBS and MS patients (3.55 nM vs. 2.6 nM). uPA was detectable in a minority of patients (15% of GBS, 20% if MS and 7% of non-inflammatory diseases), and tPA was not detect. To further investigate the origin of plasminogen in the central nervous system, we are currently exploring the presence of plasminogen in mouse parenchyma in physiological and inflammatory conditions by immuno-histochemistry. In conclusion, we have shown that a plasminogen activation system is detectable in CSF of patient with inflammatory and non-inflammatory diseases. The role of these proteolytic messengers in diseases outcome remains to be determined.