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Mast Cell Neural Interactions in Health and Disease


Mast Cell Neural Interactions in Health and Disease

Aditya Mittal et al. Front Cell Neurosci.


Mast cells (MCs) are located in the periphery as well as the central nervous system (CNS). Known for sterile inflammation, MCs play a critical role in neuroinflammation, which is facilitated by their close proximity to nerve fibers in the periphery and meninges of the spinal cord and the brain. Multifaceted activation of MCs releasing neuropeptides, cytokines and other mediators has direct effects on the neural system as well as neurovascular interactions. Emerging studies have identified the release of extracellular traps, a phenomenon traditionally meant to ensnare invading pathogens, as a cause of MC-induced neural injury. In this review article, we will discuss mechanisms of MC interaction with the nervous system through degranulation, de novo synthesis, extracellular vesicles (EVs), tunneling nanotubes, and extracellular traps with implications across a variety of pathological conditions.

Keywords: blood brain barrier; endothelial cell; inflammation; mast cell; nervous system; pain.


Figure 1
Figure 1
Mast cell (MC) activation promotes hyperalgesia in sickle cell disease (SCD). MC activation leads to the release of noxious substances such as proteases, neuropeptides and cytokines as well as the release of MC extracellular traps (MCETs) with citrullinated H3 histones and DNA, which cause noxious as well as physical injury to the vasculature and nerve bundles, leading to hyperalgesia in SCD. Emerging data suggest that this process is mediated by endoplasmic reticulum (ER) stress/reactive oxygen species (ROS) production and may engage FcεR1 and toll-like receptor 4 (TLR4) leading to Syk associated downstream protein kinase B (PKB/Akt) signaling. Consequent peptidylarginine deiminase-4 (PAD-4) activation may stimulate the release of extracellular traps, while inflammasome signaling may further augment inflammation.

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