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P2X Receptor-Dependent Modulation of Mast Cell and Glial Cell Activities in Neuroinflammation
Barbora Salcman1, Karen Affleck2, Silvia Bulfone-Paus1
1Lydia Becker Institute of Immunology and Inflammation, Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester M13 9NT, UK.
Abstract:
Localisation of mast cells (MCs) at the abluminal side of blood vessels in the brain favours their interaction with glial cells, neurons, and endothelial cells, resulting in the activation of these cells and the release of pro-inflammatory mediators. In turn, stimulation of glial cells, such as microglia, astrocytes, and oligodendrocytes may result in the modulation of MC activities. MCs, microglia, astrocytes, and oligodendrocytes all express P2X receptors (P2XRs) family members that are selectively engaged by ATP. As increased concentrations of extracellular adenosine 5'-triphosphate (ATP) are present in the brain in neuropathological conditions, P2XR activation in MCs and glial cells contributes to the control of their communication and amplification of the inflammatory response. In this review we discuss P2XR-mediated MC activation, its bi-directional effect on microglia, astrocytes and oligodendrocytes and role in neuroinflammation.
Insights
Mast cells and glial cells in the brain communicate via P2X receptors (P2XRs) activated by ATP. This interaction amplifies neuroinflammation, influencing conditions like neuropathology.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Mast cells (MCs) located near brain blood vessels interact with glial cells, neurons, and endothelial cells.
- This interaction triggers the release of pro-inflammatory mediators and can modulate MC activity through glial cell stimulation.
Purpose of the Study:
- To review the role of P2X receptors (P2XRs) in mast cell activation.
- To examine the bidirectional communication between mast cells and glial cells (microglia, astrocytes, oligodendrocytes).
- To elucidate the contribution of P2XR signaling to neuroinflammation.
Main Methods:
- Literature review focusing on P2X receptor function in neuroinflammation.
- Analysis of studies detailing mast cell and glial cell interactions.
- Examination of ATP-mediated signaling pathways.
Main Results:
- Mast cells and glial cells express P2X receptors (P2XRs) activated by extracellular adenosine 5'-triphosphate (ATP).
- Elevated ATP levels in neuropathological conditions enhance P2XR activation.
- P2XR signaling facilitates communication between mast cells and glial cells, amplifying inflammatory responses.
Conclusions:
- P2X receptor activation is a key mechanism in mast cell-mediated neuroinflammation.
- The bi-directional signaling between mast cells and glial cells via P2XRs plays a significant role in neuropathological conditions.
- Targeting P2XRs presents a potential therapeutic strategy for neuroinflammatory diseases.
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