Effect of Differently Polarized Human Macrophages on the SH-SY5Y Cells Damaged by Ischemia and Hypoxia In Vitro

Macrophages are the major cells of innate immunity with a wide range of biological effects due to their great plasticity and heterogeneity. Macrophages play a key role in neuroregeneration following nervous tissue injury. However, the neuroregenerative potential of various macrophage phenotypes, inc...

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Main Authors: Ivan Mikhailovich Rashchupkin, Ekaterina Yakovlevna Shevela, Aleksandra Aleksandrovna Maksimova, Marina Aleksandrovna Tikhonova, Aleksandr Anatolevich Ostanin, Elena Removna Chernykh
Format: Article
Language:English
Published: Hindawi Limited 2023-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2023/5595949
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author Ivan Mikhailovich Rashchupkin
Ekaterina Yakovlevna Shevela
Aleksandra Aleksandrovna Maksimova
Marina Aleksandrovna Tikhonova
Aleksandr Anatolevich Ostanin
Elena Removna Chernykh
author_facet Ivan Mikhailovich Rashchupkin
Ekaterina Yakovlevna Shevela
Aleksandra Aleksandrovna Maksimova
Marina Aleksandrovna Tikhonova
Aleksandr Anatolevich Ostanin
Elena Removna Chernykh
author_sort Ivan Mikhailovich Rashchupkin
collection DOAJ
description Macrophages are the major cells of innate immunity with a wide range of biological effects due to their great plasticity and heterogeneity. Macrophages play a key role in neuroregeneration following nervous tissue injury. However, the neuroregenerative potential of various macrophage phenotypes, including those polarized by efferocytosis, remains unexplored. The aim of this study was to compare the neuroregenerative and neuroprotective activity of soluble factors secreted by variously activated human macrophages on the functions of neural progenitors in an in vitro model of ischemia or ischemia/hypoxia. Macrophages were polarized by interferon-γ (M1), IL-4 (M2a), or interaction with apoptotic cells (M2(LS)). The effect of macrophages conditioned media on the proliferation, differentiation, and survival of SH-SY5Y cells damaged by serum deprivation alone (ischemic conditions) or in combination with CoCl2 (ischemic/hypoxic conditions) was assessed. All studied macrophages stimulated the proliferation and differentiation of SH-SY5Y cells. On day 3, the pro-proliferating effect of M1 and M2 was similar and did not depend on the severity of the damaging effect (ischemia or ischemia/hypoxia), while on day 7 and under ischemic/hypoxic conditions, the effects of M2(LS) exceeded those of M1 and M2a cells. The prodifferentiation effects of macrophages were manifested in both short- and long-term cultures, mainly under ischemic/hypoxic conditions, and were most characteristic of M2(LS) cells. Importantly, the ischemia/hypoxia model was accompanied by the pronounced death of SH-SY5Y cells. Only macrophages with the M2 phenotype demonstrated antiapoptotic activity, and the effect of M2(LS) was higher than that of M2a. The results obtained indicate that human macrophages have neuroprotective and neuroregenerative activity, which is mediated by soluble factors, is most characteristic for macrophages activated by efferocytosis (M2(LS)), and is most prominent under in vitro conditions simulating the combined effect of ischemia/hypoxia.
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spelling doaj.art-b38366cb0fe94547960081828543e7b92023-09-08T00:00:02ZengHindawi LimitedJournal of Immunology Research2314-71562023-01-01202310.1155/2023/5595949Effect of Differently Polarized Human Macrophages on the SH-SY5Y Cells Damaged by Ischemia and Hypoxia In VitroIvan Mikhailovich Rashchupkin0Ekaterina Yakovlevna Shevela1Aleksandra Aleksandrovna Maksimova2Marina Aleksandrovna Tikhonova3Aleksandr Anatolevich Ostanin4Elena Removna Chernykh5Scientific Research Institute of Fundamental and Clinical ImmunologyScientific Research Institute of Fundamental and Clinical ImmunologyScientific Research Institute of Fundamental and Clinical ImmunologyScientific Research Institute of Fundamental and Clinical ImmunologyScientific Research Institute of Fundamental and Clinical ImmunologyScientific Research Institute of Fundamental and Clinical ImmunologyMacrophages are the major cells of innate immunity with a wide range of biological effects due to their great plasticity and heterogeneity. Macrophages play a key role in neuroregeneration following nervous tissue injury. However, the neuroregenerative potential of various macrophage phenotypes, including those polarized by efferocytosis, remains unexplored. The aim of this study was to compare the neuroregenerative and neuroprotective activity of soluble factors secreted by variously activated human macrophages on the functions of neural progenitors in an in vitro model of ischemia or ischemia/hypoxia. Macrophages were polarized by interferon-γ (M1), IL-4 (M2a), or interaction with apoptotic cells (M2(LS)). The effect of macrophages conditioned media on the proliferation, differentiation, and survival of SH-SY5Y cells damaged by serum deprivation alone (ischemic conditions) or in combination with CoCl2 (ischemic/hypoxic conditions) was assessed. All studied macrophages stimulated the proliferation and differentiation of SH-SY5Y cells. On day 3, the pro-proliferating effect of M1 and M2 was similar and did not depend on the severity of the damaging effect (ischemia or ischemia/hypoxia), while on day 7 and under ischemic/hypoxic conditions, the effects of M2(LS) exceeded those of M1 and M2a cells. The prodifferentiation effects of macrophages were manifested in both short- and long-term cultures, mainly under ischemic/hypoxic conditions, and were most characteristic of M2(LS) cells. Importantly, the ischemia/hypoxia model was accompanied by the pronounced death of SH-SY5Y cells. Only macrophages with the M2 phenotype demonstrated antiapoptotic activity, and the effect of M2(LS) was higher than that of M2a. The results obtained indicate that human macrophages have neuroprotective and neuroregenerative activity, which is mediated by soluble factors, is most characteristic for macrophages activated by efferocytosis (M2(LS)), and is most prominent under in vitro conditions simulating the combined effect of ischemia/hypoxia.http://dx.doi.org/10.1155/2023/5595949
spellingShingle Ivan Mikhailovich Rashchupkin
Ekaterina Yakovlevna Shevela
Aleksandra Aleksandrovna Maksimova
Marina Aleksandrovna Tikhonova
Aleksandr Anatolevich Ostanin
Elena Removna Chernykh
Effect of Differently Polarized Human Macrophages on the SH-SY5Y Cells Damaged by Ischemia and Hypoxia In Vitro
Journal of Immunology Research
title Effect of Differently Polarized Human Macrophages on the SH-SY5Y Cells Damaged by Ischemia and Hypoxia In Vitro
title_full Effect of Differently Polarized Human Macrophages on the SH-SY5Y Cells Damaged by Ischemia and Hypoxia In Vitro
title_fullStr Effect of Differently Polarized Human Macrophages on the SH-SY5Y Cells Damaged by Ischemia and Hypoxia In Vitro
title_full_unstemmed Effect of Differently Polarized Human Macrophages on the SH-SY5Y Cells Damaged by Ischemia and Hypoxia In Vitro
title_short Effect of Differently Polarized Human Macrophages on the SH-SY5Y Cells Damaged by Ischemia and Hypoxia In Vitro
title_sort effect of differently polarized human macrophages on the sh sy5y cells damaged by ischemia and hypoxia in vitro
url http://dx.doi.org/10.1155/2023/5595949
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