title: Suppression of Brain Mast Cells Degranulation Inhibits Microglial Activation and Central Nervous System Inflammation.
abstract: Brain inflammation has a critical role in the pathophysiology of brain diseases. Microglia, the resident immune cells in the brain, play an important role in brain inflammation, while brain mast cells are the "first responder" in the injury rather than microglia. Functional aspects of mast cell-microglia interactions remain poorly understood. Our results demonstrated that site-directed injection of the "mast cell degranulator" compound 48/80 (C48/80) in the hypothalamus induced mast cell degranulation, microglial activation, and inflammatory factor production, which initiated the acute brain inflammatory response. "Mast cell stabilizer" disodium cromoglycate (cromolyn) inhibited this effect, including decrease of inflammatory cytokines, reduced microglial activation, inhibition of MAPK and AKT pathways, and repression of protein expression of histamine receptor 1 (H1R), histamine receptor 4 (H4R), protease-activated receptor 2 (PAR2), and toll-like receptor 4 (TLR4) in microglia. We also demonstrated that C48/80 had no effect on microglial activation in mast cell-deficient KitW-sh/W-shmice. These results implicate that activated brain mast cells trigger microglial activation and stabilization of mast cell inhibits microglial activation-induced central nervous system (CNS) inflammation. Interactions between mast cells and microglia could constitute a new and unique therapeutic target for CNS immune inflammation-related diseases.
authors.affiliation: Clinical Research Center, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China.|Department of Anesthesiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Hongquan
authors.initials: H
authors.lastname: Dong
authors.affiliation: Clinical Research Center, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China.|Department of Anesthesiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Clinical Research Center, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Xiqiao
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Clinical Research Center, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China. zszqs@hotmail.com.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism*; D015550:Cell Degranulation / Q000502:physiology*; D007031:Hypothalamus / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008262:Macrophage Activation / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: CNS immune inflammation; Compound 48/80; Cromolyn; Mast cell degranulation; Microglial activation