Abstract
Microglial activation by purines and pyrimidines is reviewed, with emphasis on the actions of adenosine 5โฒโtriphosphate (ATP) on chemotaxis or releases of plasminogen and cytokines from microglia. ATP activates microglia, causing morphological changes with membrane ruffling. Activated microglia exhibit chemotaxis to ATP. Microglia stimulated by a low concentration of ATP (โผ30โ50 ฮผM) rapidly release plasminogen (within 5โ10 min), which may protect neurons. Microglia stimulated by a higher concentration of ATP release tumor necrosis factorโฮฑ (TNFโฮฑ), 2โ3 h after the stimulation and interleukinโ6 (ILโ6), 6 h after the stimulation. It is reported that TNFโฮฑ stimulation causes an increase in the expression of ILโ6 receptor mRNA and expression in neuronal cells (Mรคrz et al. 1996. Brain Res 706:71โ79). After binding with gp130, the ILโ6 receptor matures and can accept ILโ6 molecules. It is speculated that neurons may require several hours to prepare for the full reception of ILโ6, which induces a more efficient protective effect by ILโ6 after stimulation with TNFโฮฑ. After neurons are ready to accept ILโ6 fully, microglia release ILโ6 to neurons. Stronger and longer stimulation by ATP may change the function of microglia and cause cell death. The conditions evoking the heavy stimulation would result from serious injury. Activated microglia act as scavenger cells that induce apoptosis in damaged neurons by releasing toxic factors, including NO, and removing dead cells, their remnants, or dangerous debris by phagocytosis. These actions lead to a suitable environment for tissue repair and neural regeneration. The fate of neurons may therefore be regulated in part by ATP through the activation of microglia. GLIA 40:156โ163, 2002. ยฉ 2002 WileyโLiss, Inc.