Significance of microglia derived plasmin-generating proteases in the nervous system

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The aim of this study was to study (1) action mechanism of plasminogen in the neuron, (2) production of microglia-derived proteases in the brain, (3) regulatory factor of secretory proteases from microglia.(1) We studied the action of plasminogen and prodiction of inositol tri-phosphate (IP3) or protein-phosphorylations in the cultured neuron derived from neonatal rat brain, and found taht plasminogen induces a transiient increase of IP3 and causes a tyrosine- phosphorylation in a certain protein(>100kDa) of cultured neuron. However, since, in the latter case, the degree of phophorylation was very low and delicate, it is necessary to be confirmed by trustworthy study.(2) Using the transection model of rat facial nerve, we showed taht plasminogen activator activity was transiently induced in axotomized facial nucleus. The plasminogen activator was characterized and identified as urokinase type plasminogen activator (uPA) from the results of response to the uPA inhibitor, amiloride, and of the molecular weight. The cell producing uPA in the facial nucleus was sugested to be microglia. Plasminogen was also suggested to increase in axotomized facial nucleus.(3) We surveyed the factors which elevate the amounts of plasminogen and/or plasminogen activator in microglia, and found that neurotrophin has an ability to promote the secretion of plasminogen and uPA.Nerve growth factor, brain-derived neurotrophic factor, neurotrophon-3 and neurotrophin-4/5 were comparable for the increasing effect. The neurotrophin had a capacity to decrease the release of nitric oxide from microglia. The analysis of specific receptor for the neurotrophins in cultured microglia revealed the expression of trk A,trk B and trk C at both mRNA and protein level.