Neurotransmitter and neuropeptide regulation of mast cell function: a systematic review
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REVIEW
Open Access
Neurotransmitter and neuropeptide regulation of mast cell function: a systematic review Huaping Xu1, Xiaoyun Shi2, Xin Li3, Jiexin Zou4, Chunyan Zhou5, Wenfeng Liu5, Huming Shao5, Hongbing Chen5 and Linbo Shi4*
Abstract The existence of the neural control of mast cell functions has long been proposed. Mast cells (MCs) are localized in association with the peripheral nervous system (PNS) and the brain, where they are closely aligned, anatomically and functionally, with neurons and neuronal processes throughout the body. They express receptors for and are regulated by various neurotransmitters, neuropeptides, and other neuromodulators. Consequently, modulation provided by these neurotransmitters and neuromodulators allows neural control of MC functions and involvement in the pathogenesis of mast cell–related disease states. Recently, the roles of individual neurotransmitters and neuropeptides in regulating mast cell actions have been investigated extensively. This review offers a systematic review of recent advances in our understanding of the contributions of neurotransmitters and neuropeptides to mast cell activation and the pathological implications of this regulation on mast cell–related disease states, though the full extent to which such control influences health and disease is still unclear, and a complete understanding of the mechanisms underlying the control is lacking. Future validation of animal and in vitro models also is needed, which incorporates the integration of microenvironment-specific influences and the complex, multifaceted cross-talk between mast cells and various neural signals. Moreover, new biological agents directed against neurotransmitter receptors on mast cells that can be used for therapeutic intervention need to be more specific, which will reduce their ability to support inflammatory responses and enhance their potential roles in protecting against mast cell–related pathogenesis. Keywords: Neuron-mast cell interaction, Neurotransmitters, Neuropeptides
Background Both the nervous and immune systems play critical roles in regulating processes required to protect against external threats, respond to acute stressors, and maintain physiological homeostasis [1]. As “first responders” of the immune system, MCs are omnipresent in the body. They are localized in association with PNS and the brain, where they are closely aligned, anatomically and * Correspondence: [email protected] 4 Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Nanchang University, 461 Bayi Avenue, Nanchang 330006, Jiangxi Province, People’s Republic of China Full list of author information is available at the end of the article
functionally, with neurons and neuronal processes throughout the body. MC numbers are particularly high in tissues innervated by small-caliber sensory A-delta and C-fibers, which are responsible for pain transmission; the close anatomic associations between MCs and nerves are especially evident at sites of inflammation [2, 3]. Thus, the existe
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