title: Mast Cells Release Chemokine CCL2 in Response to Parkinsonian Toxin 1-Methyl-4-Phenyl-Pyridinium (MPP(+)).
abstract: Microglial activation and release of inflammatory cytokines and chemokines are crucial events in neuroinflammation. Microglial cells interact and respond to other inflammatory cells such as T cells and mast cells as well as inflammatory mediators secreted from these cells. Recent studies have shown that neuroinflammation causes and accelerates neurodegenerative disease such as Parkinson's disease (PD) pathogenesis. 1-methyl-4-phenyl-pyridinium ion (MPP(+)), the active metabolite of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine activates glial cells and mediate neurodegeneration through release of inflammatory mediators. We have shown that glia maturation factor (GMF) activates glia and induces neuroinflammation and neurodegeneration and that MPP(+) activates mast cells and release proinflammatory cytokines and chemokines. The chemokine (C-C motif) ligand 2 (CCL2) levels have been shown to be elevated and play a role in PD pathogenesis. In the present study, we analyzed if MPP(+) activates mouse and human mast cells to release chemokine CCL2. Mouse bone marrow-derived mast cells (BMMCs) and human umbilical cord blood-derived cultured mast cells (hCBMCs) were incubated with MPP(+) (10 µM) for 24 h and CCL2 levels were measured in the supernatant media by ELISA. MPP(+)-significantly induced CCL2 release from BMMCs and hCBMCs. Additionally, GMF overexpression in BMMCs obtained from wild-type mice released significantly more CCL2, while BMMCs obtained from GMF-deficient mice showed less CCL2 release. Further, we show that MPP(+)-induced CCL2 release was greater in BMMCs-astrocyte co-culture conditions. Uncoupling protein 4 (UCP4) which is implicated in neurodegenerative diseases including PD was detected in BMMCs by immunocytochemistry. Our results suggest that mast cells may play role in PD pathogenesis.
authors.affiliation: Veterans Affairs Health Care System, Iowa City, IA, 52242, USA.|Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA.
authors.forename: Duraisamy
authors.initials: D
authors.lastname: Kempuraj
authors.affiliation: Veterans Affairs Health Care System, Iowa City, IA, 52242, USA.|Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA.
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Thangavel
authors.affiliation: Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA.
authors.forename: Ranan
authors.initials: R
authors.lastname: Fattal
authors.affiliation: Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA.
authors.forename: Sagar
authors.initials: S
authors.lastname: Pattani
authors.affiliation: Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA.
authors.forename: Evert
authors.initials: E
authors.lastname: Yang
authors.affiliation: Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA.
authors.forename: Smita
authors.initials: S
authors.lastname: Zaheer
authors.affiliation: Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA.
authors.forename: Donna A
authors.initials: DA
authors.lastname: Santillan
authors.affiliation: Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA.
authors.forename: Mark K
authors.initials: MK
authors.lastname: Santillan
authors.affiliation: Veterans Affairs Health Care System, Iowa City, IA, 52242, USA. asgar-zaheer@uiowa.edu.|Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA. asgar-zaheer@uiowa.edu.
authors.forename: Asgar
authors.initials: A
authors.lastname: Zaheer
mesh_terms: D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D018920:Coculture Techniques; D005312:Fetal Blood / Q000166:cytology; D020904:Glia Maturation Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D000071245:Mitochondrial Uncoupling Proteins / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2; D020904:Glia Maturation Factor; D000071245:Mitochondrial Uncoupling Proteins; C547516:Slc25a27 protein, mouse; D015655:1-Methyl-4-phenylpyridinium
keywords: 1-Methyl-4-phenyl-pyridinium; CCL2; Glia maturation factor; Mast cells; Parkinson’s disease