Molecular and Cellular Impact of Inflammatory Extracellular Vesicles (EVs) Derived from M1 and M2 Macrophages on Neural Action Potentials

Several factors can contribute to neuroinflammatory disorders, such as cytokine and chemokines that are produced and released from peripherally derived immune cells or from locally activated cells such as microglia and perivascular macrophages in the brain. The primary function of these cells is to...

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Main Authors: Sarah Vakili, Taha Mohseni Ahooyi, Shadan S. Yarandi, Martina Donadoni, Jay Rappaport, Ilker K. Sariyer
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:Brain Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3425/10/7/424
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author Sarah Vakili
Taha Mohseni Ahooyi
Shadan S. Yarandi
Martina Donadoni
Jay Rappaport
Ilker K. Sariyer
author_facet Sarah Vakili
Taha Mohseni Ahooyi
Shadan S. Yarandi
Martina Donadoni
Jay Rappaport
Ilker K. Sariyer
author_sort Sarah Vakili
collection DOAJ
description Several factors can contribute to neuroinflammatory disorders, such as cytokine and chemokines that are produced and released from peripherally derived immune cells or from locally activated cells such as microglia and perivascular macrophages in the brain. The primary function of these cells is to clear inflammation; however, following inflammation, circulating monocytes are recruited to the central nervous system (CNS). Monocyte-derived macrophages in the CNS play pivotal roles in mediating neuroinflammatory responses. Macrophages are heterogeneous both in normal and in pathological conditions due to their plasticity, and they are classified in two main subsets, classically activated (M1) or alternatively activated (M2). There is accumulating evidence suggesting that extracellular vesicles (EVs) released from activated immune cells may play crucial roles in mediating inflammation. However, a possible role of EVs released from immune cells such as M1 and M2 macrophages on neuronal functions in the brain is not known. In order to investigate the molecular and cellular impacts of macrophages and EVs released from macrophage subtypes on neuronal functions, we used a recently established in vitro M1 and M2 macrophage culture model and isolated and characterized EVs from these macrophage subtypes, treated primary neurons with M1 or M2 EVs, and analyzed the extracellular action potentials of neurons with microelectrode array studies (MEA). Our results introduce evidence on the interfering role of inflammatory EVs released from macrophages in interneuronal signal transmission processes, with implications in the pathogenesis of neuroinflammatory diseases induced by a variety of inflammatory insults.
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spelling doaj.art-2525f8f8c87741e0ab050d8ba3f92a002023-11-20T05:45:00ZengMDPI AGBrain Sciences2076-34252020-07-0110742410.3390/brainsci10070424Molecular and Cellular Impact of Inflammatory Extracellular Vesicles (EVs) Derived from M1 and M2 Macrophages on Neural Action PotentialsSarah Vakili0Taha Mohseni Ahooyi1Shadan S. Yarandi2Martina Donadoni3Jay Rappaport4Ilker K. Sariyer5Department of Neuroscience and Center for Neurovirology, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USADepartment of Neuroscience and Center for Neurovirology, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USADepartment of Neuroscience and Center for Neurovirology, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USADepartment of Neuroscience and Center for Neurovirology, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USATulane National Primate Research Center, New Orleans, Covington, LA 70433, USADepartment of Neuroscience and Center for Neurovirology, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USASeveral factors can contribute to neuroinflammatory disorders, such as cytokine and chemokines that are produced and released from peripherally derived immune cells or from locally activated cells such as microglia and perivascular macrophages in the brain. The primary function of these cells is to clear inflammation; however, following inflammation, circulating monocytes are recruited to the central nervous system (CNS). Monocyte-derived macrophages in the CNS play pivotal roles in mediating neuroinflammatory responses. Macrophages are heterogeneous both in normal and in pathological conditions due to their plasticity, and they are classified in two main subsets, classically activated (M1) or alternatively activated (M2). There is accumulating evidence suggesting that extracellular vesicles (EVs) released from activated immune cells may play crucial roles in mediating inflammation. However, a possible role of EVs released from immune cells such as M1 and M2 macrophages on neuronal functions in the brain is not known. In order to investigate the molecular and cellular impacts of macrophages and EVs released from macrophage subtypes on neuronal functions, we used a recently established in vitro M1 and M2 macrophage culture model and isolated and characterized EVs from these macrophage subtypes, treated primary neurons with M1 or M2 EVs, and analyzed the extracellular action potentials of neurons with microelectrode array studies (MEA). Our results introduce evidence on the interfering role of inflammatory EVs released from macrophages in interneuronal signal transmission processes, with implications in the pathogenesis of neuroinflammatory diseases induced by a variety of inflammatory insults.https://www.mdpi.com/2076-3425/10/7/424M1and M2 macrophagesCD163exosomesaction potentialneuroinflammation
spellingShingle Sarah Vakili
Taha Mohseni Ahooyi
Shadan S. Yarandi
Martina Donadoni
Jay Rappaport
Ilker K. Sariyer
Molecular and Cellular Impact of Inflammatory Extracellular Vesicles (EVs) Derived from M1 and M2 Macrophages on Neural Action Potentials
Brain Sciences
M1and M2 macrophages
CD163
exosomes
action potential
neuroinflammation
title Molecular and Cellular Impact of Inflammatory Extracellular Vesicles (EVs) Derived from M1 and M2 Macrophages on Neural Action Potentials
title_full Molecular and Cellular Impact of Inflammatory Extracellular Vesicles (EVs) Derived from M1 and M2 Macrophages on Neural Action Potentials
title_fullStr Molecular and Cellular Impact of Inflammatory Extracellular Vesicles (EVs) Derived from M1 and M2 Macrophages on Neural Action Potentials
title_full_unstemmed Molecular and Cellular Impact of Inflammatory Extracellular Vesicles (EVs) Derived from M1 and M2 Macrophages on Neural Action Potentials
title_short Molecular and Cellular Impact of Inflammatory Extracellular Vesicles (EVs) Derived from M1 and M2 Macrophages on Neural Action Potentials
title_sort molecular and cellular impact of inflammatory extracellular vesicles evs derived from m1 and m2 macrophages on neural action potentials
topic M1and M2 macrophages
CD163
exosomes
action potential
neuroinflammation
url https://www.mdpi.com/2076-3425/10/7/424
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