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

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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.

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Acknowledgments

This material is based upon work supported, in part, by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development (BX002477-01, A.Z.), and by the National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke Grant NS073670 (A.Z.), and the Reproductive Scientist Development Program HD000849, RR024980 (MS) and CSTA U54TR001013. The Maternal Fetal Tissue Bank at the University of Iowa is supported by the University of Iowa Carver College of Medicine and Department of Obstetrics & Gynecology.

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Authors and Affiliations

  1. Veterans Affairs Health Care System, Iowa City, IA, 52242, USA

    Duraisamy Kempuraj, Ramasamy Thangavel & Asgar Zaheer

  2. Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA

    Duraisamy Kempuraj, Ramasamy Thangavel, Ranan Fattal, Sagar Pattani, Evert Yang, Smita Zaheer & Asgar Zaheer

  3. Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA

    Donna A. Santillan & Mark K. Santillan

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  1. Duraisamy Kempuraj
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Correspondence to Asgar Zaheer.

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Kempuraj, D., Thangavel, R., Fattal, R. et al. Mast Cells Release Chemokine CCL2 in Response to Parkinsonian Toxin 1-Methyl-4-Phenyl-Pyridinium (MPP+). Neurochem Res 41, 1042–1049 (2016). https://doi.org/10.1007/s11064-015-1790-z

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