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Schindler et al. Neuroimmunol Neuroinflammation 2016;3:232-42 Neuroimmunology and
DOI: 10.20517/2347-8659.2016.25
Neuroinflammation

www.nnjournal.net
Original Article Open Access

Possible role of microparticles in

neuroimmune signaling of microglial cells

Stephanie M. Schindler , Ekta Bajwa , Jonathan P. Little , Andis Klegeris 1
2
1*
1*
1 Department of Biology, University of British Columbia Okanagan Campus, Kelowna, British Columbia V1V 1V7, Canada.
2 School of Health and Exercise Sciences, University of British Columbia Okanagan Campus, Kelowna, British Columbia V1V 1V7, Canada.
*These authors contributed equally to this work.
Correspondence to: Dr. Andis Klegeris, Department of Biology, University of British Columbia Okanagan Campus, 3187 University Way,
Kelowna, British Columbia V1V 1V7, Canada. E-mail: andis.klegeris@ubc.ca
How to cite this article: Schindler SM, Bajwa E, Little JP, Klegeris A. Possible role of microparticles in neuroimmune signaling of microglial cells.
Neuroimmunol Neuroinflammation 2016;3:232-42.
ABSTRACT
Article history: Aim: Submicron fragments termed microparticles (MPs), derived from all major central
Received: 27-05-2016 nervous system cell types including neurons and glia (microglia, astrocytes, oligodendrocytes),
Accepted: 01-09-2016 have emerged as novel intercellular signaling agents. This study tested the hypothesis that MPs
Published: 28-10-2016 derived from activated microglia, which represent the mononuclear phagocyte system in the
brain, could induce pro-inflammatory and cytotoxic responses of microglia in an autocrine
Key words: or paracrine manner. Methods: Human THP-1 monocytic cells were used to model human
Microparticles, microglia. MPs derived from these cells were reapplied to THP-1 cells and their secretion of
damage-associated molecular neurotoxins and cytokines was measured. Results: When exposed to lipopolysaccharide (LPS)
patterns, or mitochondrial transcription factor A in combination with interferon (IFN)-γ, THP-1 cells
mononuclear phagocytes, released MPs. When reapplied to THP-1 cells, MPs induced the release of secretions that were
glial cells, toxic to human SH-SY5Y neuroblastoma cells, as well as monocyte chemoattractant protein-1.
microglia, The cytotoxicity of THP-1 cells induced by MPs derived from IFN-γ plus LPS-treated THP-1
neurotoxicity, donor cells was enhanced in the presence of IFN-γ. The MPs released by THP-1 cells were
not directly toxic towards SH-SY5Y cells. Conclusion: Our data support the hypothesis that
Alzheimer’s disease,
Parkinson’s disease activated microglia-derived MPs could act as signaling agents that are recognized by microglia
to cause pro-inflammatory and cytotoxic responses.
INTRODUCTION formations associated with central nervous system
(CNS) disorders including the amyloid-beta (Aβ) and
Microglia are a distinct population of mononuclear α-synuclein aggregates observed in Alzheimer’s and
phagocytes that represent the innate immune system Parkinson’s disease respectively can contribute to
in the brain. Under physiological conditions, the disease progression. [3,4] The state of prolonged over-
[1]
phagocytic responses of microglia ensure proper activation of microglia is characterized by increased
functioning of neuronal cells as they remove harmful secretion of pro-inflammatory cytokines as well as
material and repair injured tissue. However, chronic reactive oxygen and nitrogen species. [5-9] Similar
[2]
activation of microglia, due to recognition of pathological adverse activation of microglia occurs in response
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