Microglia Secrete Plasminogen Which Enhances the Maturation of Mesencephalic Dopaminergic Neurons in Vitro
In recent years, it has been generally accepted that survival, growth and function of neurons are regulated by neuron-glia interactions which are mediated through a variety of active substances such as neurotrophic factors, cytokines and other proteins. We recently found that a conditioned medium of cultured microglia showed neurotrophic activity for neocortical1 and mesencephalic2 neurons, suggesting that microglia secrete certain neurotrophic factor(s). During a survey of the factor(s) from microglia, certain proteases were found to be produced. Thus far elastase3, uPA4 and plasminogen (PGn)5’6 have been identified. Surprisingly, among these proteases, PGn showed neurotrophic activity such as promotion of neurite outgrowth7 and enhancement of survival and/or maturation of dopaminergic neurons. Furthermore, pharmacological study using 1251-PGn revealed that PGn specifically binds to neocortical neurons. These results strongly suggest that microglia-secretory PGn binds to specific receptor molecule(s) on the neuronal surface and elicits neuronal responses.
KeywordsTyrosine Hydroxylase Hank Balance Salt Solution Dopamine Uptake Glutamate NMDA Receptor Neurotrophic Activity
Unable to display preview. Download preview PDF.
- 1.K. Nakajima, M. Hamanoue, M. Shimojo, N. Takei, and S. Kohsaka, Characterization of microglia isolated from a primary culture of embryonic rat brain by a simplified method, Biomed. Res. 10 (S3): 411–423 (1989).Google Scholar
- 8.S. Saitoh, N. Iijima, M. Ikeda, K. Nakajima, M. Kimura, M. Katsuki, T. Mori, and S. Kohsaka, De novo production of a2 macroglobulin in cultured astroglia from rat brain, Mol. Brain Res. 12: 155–161 (1992).Google Scholar