Dopaminergic Toxin 1-Methyl-4-Phenylpyridinium, Proteins α-Synuclein and Glia Maturation Factor Activate Mast Cells and Release Inflammatory Mediators

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

doi:10.1371/journal.pone.0135776

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Dopaminergic Toxin 1-Methyl-4-Phenylpyridinium, Proteins α-Synuclein and Glia Maturation Factor Activate Mast Cells and Release Inflammatory Mediators

Journal article

Open access

Peer reviewed

Dopaminergic Toxin 1-Methyl-4-Phenylpyridinium, Proteins α-Synuclein and Glia Maturation Factor Activate Mast Cells and Release Inflammatory Mediators

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

PloS one, Vol.10(8), pp.e0135776-e0135776

2015

DOI: 10.1371/journal.pone.0135776

PMCID: PMC4537263

PMID: 26275153

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Abstract

Parkinson's disease (PD) is characterized by the presence of Lewy bodies and degeneration of dopaminergic neurons. 1-methyl-4-phenylpyridinium (MPP+), a metabolite of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and Lewy body component α-synuclein activates glia in PD pathogenesis. Mast cells and glia maturation factor (GMF) are implicated in neuroinflammatory conditions including Multiple Sclerosis. However, the role of mast cells in PD is not yet known. We have analyzed the effect of recombinant GMF, MPP+, α-synuclein and interleukin-33 (IL-33) on mouse bone marrow-derived cultured mast cells (BMMCs), human umbilical cord blood-derived cultured mast cells (hCBMCs) and mouse brain-derived cultured astrocytes by quantifying cytokines/chemokines released using ELISA or by detecting the expression of co-stimulatory molecules CD40 and CD40L by flow cytometry. GMF significantly released chemokine (C-C motif) ligand 2 (CCL2) from BMMCs but its release was reduced in BMMCs from GMF knockout mice. GMF, α-synuclein and MPP+ released IL-1β, β-hexosaminidase from BMMCs, and IL-8 from hCBMCs. GMF released CCL5, and IL-33- induced the expression of GMF from hCBMCs. Novel GMF expression was detected in hCBMCs and BMMCs by immunocytochemistry. GMF released tumor necrosis factor-alpha (TNF-α) from mouse astrocytes, and this release was greater in BMMC- astrocyte coculture than in individual cultures. Flow cytometry results showed increased IL-33 expression by GMF and MPP+, and GMF-induced CD40 expression in astrocytes. Proinflammatory mediator release by GMF, MPP+ and α-synuclein, as well as GMF expression by mast cells indicate a potential therapeutic target for neurodegenerative diseases including PD.

Astrocytes - drug effects

Enzyme-Linked Immunosorbent Assay

Interleukin-33 - pharmacology

1-Methyl-4-phenylpyridinium - pharmacology

Humans

Cells, Cultured

Glia Maturation Factor - pharmacology

Male

Mast Cells - drug effects

Pregnancy

Animals

CD40 Antigens - metabolism

CD40 Ligand - metabolism

Flow Cytometry

Mast Cells - metabolism

Female

Mice

Interleukin-8 - metabolism

alpha-Synuclein - metabolism

Astrocytes - metabolism

Details

Title: Subtitle: Dopaminergic Toxin 1-Methyl-4-Phenylpyridinium, Proteins α-Synuclein and Glia Maturation Factor Activate Mast Cells and Release Inflammatory Mediators
Creators: Duraisamy Kempuraj - Veterans Affairs Health Care System, Iowa City, Iowa, United States of America; Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States of America
Ramasamy Thangavel - Veterans Affairs Health Care System, Iowa City, Iowa, United States of America; Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States of America
Evert Yang - Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States of America
Sagar Pattani - Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States of America
Smita Zaheer - Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States of America
Donna A Santillan - Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States of America
Mark K Santillan - Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States of America
Asgar Zaheer - Veterans Affairs Health Care System, Iowa City, Iowa, United States of America; Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States of America
Resource Type: Journal article
Publication Details: PloS one, Vol.10(8), pp.e0135776-e0135776
DOI: 10.1371/journal.pone.0135776
PMID: 26275153
PMCID: PMC4537263
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
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: 2015
Academic Unit: Neurology; Obstetrics and Gynecology
Record Identifier: 9983931384702771

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