Mast Cells Release Chemokine CCL2 in Response to Parkinsonian Toxin 1-Methyl-4-Phenyl-Pyridinium (MPP(+))

Duraisamy Kempuraj; Ramasamy Thangavel; Ranan Fattal; Sagar Pattani; Evert Yang; Smita Zaheer; Donna A Santillan; Mark K Santillan; Asgar Zaheer

doi:10.1007/s11064-015-1790-z

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Mast Cells Release Chemokine CCL2 in Response to Parkinsonian Toxin 1-Methyl-4-Phenyl-Pyridinium (MPP(+))

Journal article

Open access

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Mast Cells Release Chemokine CCL2 in Response to Parkinsonian Toxin 1-Methyl-4-Phenyl-Pyridinium (MPP(+))

Duraisamy Kempuraj, Ramasamy Thangavel, Ranan Fattal, Sagar Pattani, Evert Yang, Smita Zaheer, Donna A Santillan, Mark K Santillan and Asgar Zaheer

Neurochemical research, Vol.41(5), pp.1042-1049

05/2016

DOI: 10.1007/s11064-015-1790-z

PMCID: PMC4834226

PMID: 26646004

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http://doi.org/10.1007/s11064-015-1790-zView

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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.

Glia Maturation Factor - genetics

Chemokine CCL2 - secretion

Coculture Techniques

Humans

Cells, Cultured

Fetal Blood - cytology

Mice, Knockout

Mitochondrial Uncoupling Proteins - metabolism

Animals

Glia Maturation Factor - metabolism

1-Methyl-4-phenylpyridinium

Mast Cells - secretion

Mice

Parkinson Disease - metabolism

Astrocytes - metabolism

Parkinson Disease - etiology

Details

Title: Subtitle: Mast Cells Release Chemokine CCL2 in Response to Parkinsonian Toxin 1-Methyl-4-Phenyl-Pyridinium (MPP(+))
Creators: Duraisamy Kempuraj - Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA
Ramasamy Thangavel - Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA
Ranan Fattal - Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA
Sagar Pattani - Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA
Evert Yang - Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA
Smita Zaheer - Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA
Donna A Santillan - Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA
Mark K Santillan - Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA
Asgar Zaheer - Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA. asgar-zaheer@uiowa.edu
Resource Type: Journal article
Publication Details: Neurochemical research, Vol.41(5), pp.1042-1049
DOI: 10.1007/s11064-015-1790-z
PMID: 26646004
PMCID: PMC4834226
NLM abbreviation: Neurochem Res
ISSN: 0364-3190
eISSN: 1573-6903
Publisher: United States
Grant note: RR024980 / NCRR NIH HHS K12 HD000849 / NICHD NIH HHS I01 BX002477 / BLRD VA U54 TR001013 / NCATS NIH HHS HD000849 / NICHD NIH HHS U54TR001013 / NCATS NIH HHS NS073670 / NINDS NIH HHS R01 NS073670 / NINDS NIH HHS KL2 RR024980 / NCRR NIH HHS
Language: English
Date published: 05/2016
Academic Unit: Neurology; Obstetrics and Gynecology
Record Identifier: 9983931171102771

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