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1
Consiglio Nazionale delle Ricerche Cellular and Molecular Pharmacology and "B. Ceccarelli" Centers, Department of Medical Pharmacology, Milan, Italy
Calcium-mediated intercellular communication is a mechanism by
which astrocytes communicate with each other and modulate the activity
of adjacent cells, including neurons and oligodendrocytes. We have
investigated whether microglia, the immune effector cells involved in
several diseases of the CNS, are actively involved in this
communication network. To address this issue, we analyzed calcium
dynamics in fura-2-loaded cocultures of astrocytes and microglia under
physiological conditions and in the presence of the inflammatory
cytokine IFN-
. The intracellular calcium increases in astrocytes,
occurring spontaneously or as a result of mechanical or bradykinin
stimulation, induced the release of ATP, which, in turn, was
responsible for triggering a delayed calcium response in microglial
cells. Repeated stimulations of microglial cells by astrocyte-released
ATP activated P2X7 purinergic receptor on microglial cells
and greatly increased membrane permeability, eventually leading to
microglial apoptosis. IFN- increased ATP release and potentiated the
P2X7-mediated cytolytic effect. This is the first study
showing that ATP mediates a form of calcium signaling between
astrocytes and microglia. This mechanism of intercellular communication
may be involved in controlling the number and function of microglial
cells under pathophysiologic CNS conditions.
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 H. Sauer, R. Stanelle, J. Hescheler, and M. Wartenberg The DC electrical-field-induced Ca2+ response and growth stimulation of multicellular tumor spheroids are mediated by ATP release and purinergic receptor stimulation J. Cell Sci., August 15, 2002; 115(16): 3265 - 3273. [Abstract] [Full Text] [PDF]
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J. M. Labasi, N. Petrushova, C. Donovan, S. McCurdy, P. Lira, M. M. Payette, W. Brissette, J. R. Wicks, L. Audoly, and C. A. Gabel Absence of the P2X7 Receptor Alters Leukocyte Function and Attenuates an Inflammatory Response J. Immunol., June 15, 2002; 168(12): 6436 - 6445. [Abstract] [Full Text] [PDF]
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