Distinct Polarization Dynamics of Microglia and Infiltrating Macrophages: A Novel Mechanism of Spinal Cord Ischemia/Reperfusion Injury

Hui Li,1,2 Pengfei Wang,1,2 Lin Tang,1,2 Jingjing Sun,1,2 Yanling Zhang,1,2 Wei Luo,1,2 Cong Luo,1,2 Zhaolan Hu,1,2 Lin Yang1,2 1Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Hunan Province Center for Clinical Anesthesia a...

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Autores principales:	Li H, Wang P, Tang L, Sun J, Zhang Y, Luo W, Luo C, Hu Z, Yang L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	spinal cord ischemia/reperfusion injury microglia monocyte derived macrophages polarization inflammation Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/4a7a1dfd752841e5a5ee4a974af5524a
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spelling	oai:doaj.org-article:4a7a1dfd752841e5a5ee4a974af5524a2021-12-02T19:15:19ZDistinct Polarization Dynamics of Microglia and Infiltrating Macrophages: A Novel Mechanism of Spinal Cord Ischemia/Reperfusion Injury1178-7031https://doaj.org/article/4a7a1dfd752841e5a5ee4a974af5524a2021-10-01T00:00:00Zhttps://www.dovepress.com/distinct-polarization-dynamics-of-microglia-and-infiltrating-macrophag-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Hui Li,1,2 Pengfei Wang,1,2 Lin Tang,1,2 Jingjing Sun,1,2 Yanling Zhang,1,2 Wei Luo,1,2 Cong Luo,1,2 Zhaolan Hu,1,2 Lin Yang1,2 1Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Hunan Province Center for Clinical Anesthesia and Anesthesiology, Research Institute of Central South University, Changsha, People’s Republic of ChinaCorrespondence: Lin YangDepartment of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaFax +86 73185295970Email linyang@csu.edu.cnPurpose: Recent studies indicate that microglia and monocyte-derived macrophages (MDMs) have different roles in diseases such as stroke and spinal cord injury, yet their respective polarized phenotypes and roles remain unclear in spinal cord ischemia/reperfusion injury (SCIRI).Methods: We established a mouse model of SCIRI by transient aortic occlusion followed by reperfusion. Basso mouse scale (BMS) scores were used to test the locomotor functions. The histopathological changes in spinal cord were assessed by hematoxylin-eosin staining and NF-200 immunohistochemistry. Real-time PCR, immunofluorescence and flow cytometry were employed to analyze the polarized phenotypes of the microglia and infiltrating MDMs, and the resulting inflammatory responses. Furthermore, the role of infiltrating MDMs were investigated by MDMs depletion using systemic administration of clodronate-liposomes.Results: SCIRI significantly impaired locomotor function of mice, accompanied with progressed necrosis, infiltration of inflammatory cells and neuron loss in the spinal cord. M1-related pro-inflammatory markers (iNOS, CD16, CD86 and TNF-α) increased dramatically in the early phase following SCIRI. In contrast, M2-related anti-inflammatory markers (CD204 and CD206) elevated at later stage. Besides, the invading MDMs were principally pro-inflammatory M1 type, transiently restricted to the first week after SCIRI. In contrast, microglia were the main source of anti-inflammatory M2 type. Furthermore, depletion of MDMs by clodronate-liposomes significantly preserved neurological functions and relieved neuronal damage caused by SCIRI.Conclusion: These findings suggested distinct polarized status of resident microglia and MDMs following SCIRI. Inhibition of the invading MDMs may represent a novel approach for SCIRI treatment.Keywords: spinal cord ischemia/reperfusion injury, microglia, monocyte derived macrophages, polarization, inflammationLi HWang PTang LSun JZhang YLuo WLuo CHu ZYang LDove Medical Pressarticlespinal cord ischemia/reperfusion injurymicrogliamonocyte derived macrophagespolarizationinflammationPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 5227-5239 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	spinal cord ischemia/reperfusion injury microglia monocyte derived macrophages polarization inflammation Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	spinal cord ischemia/reperfusion injury microglia monocyte derived macrophages polarization inflammation Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Li H Wang P Tang L Sun J Zhang Y Luo W Luo C Hu Z Yang L Distinct Polarization Dynamics of Microglia and Infiltrating Macrophages: A Novel Mechanism of Spinal Cord Ischemia/Reperfusion Injury
description	Hui Li,1,2 Pengfei Wang,1,2 Lin Tang,1,2 Jingjing Sun,1,2 Yanling Zhang,1,2 Wei Luo,1,2 Cong Luo,1,2 Zhaolan Hu,1,2 Lin Yang1,2 1Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Hunan Province Center for Clinical Anesthesia and Anesthesiology, Research Institute of Central South University, Changsha, People’s Republic of ChinaCorrespondence: Lin YangDepartment of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaFax +86 73185295970Email linyang@csu.edu.cnPurpose: Recent studies indicate that microglia and monocyte-derived macrophages (MDMs) have different roles in diseases such as stroke and spinal cord injury, yet their respective polarized phenotypes and roles remain unclear in spinal cord ischemia/reperfusion injury (SCIRI).Methods: We established a mouse model of SCIRI by transient aortic occlusion followed by reperfusion. Basso mouse scale (BMS) scores were used to test the locomotor functions. The histopathological changes in spinal cord were assessed by hematoxylin-eosin staining and NF-200 immunohistochemistry. Real-time PCR, immunofluorescence and flow cytometry were employed to analyze the polarized phenotypes of the microglia and infiltrating MDMs, and the resulting inflammatory responses. Furthermore, the role of infiltrating MDMs were investigated by MDMs depletion using systemic administration of clodronate-liposomes.Results: SCIRI significantly impaired locomotor function of mice, accompanied with progressed necrosis, infiltration of inflammatory cells and neuron loss in the spinal cord. M1-related pro-inflammatory markers (iNOS, CD16, CD86 and TNF-α) increased dramatically in the early phase following SCIRI. In contrast, M2-related anti-inflammatory markers (CD204 and CD206) elevated at later stage. Besides, the invading MDMs were principally pro-inflammatory M1 type, transiently restricted to the first week after SCIRI. In contrast, microglia were the main source of anti-inflammatory M2 type. Furthermore, depletion of MDMs by clodronate-liposomes significantly preserved neurological functions and relieved neuronal damage caused by SCIRI.Conclusion: These findings suggested distinct polarized status of resident microglia and MDMs following SCIRI. Inhibition of the invading MDMs may represent a novel approach for SCIRI treatment.Keywords: spinal cord ischemia/reperfusion injury, microglia, monocyte derived macrophages, polarization, inflammation
format	article
author	Li H Wang P Tang L Sun J Zhang Y Luo W Luo C Hu Z Yang L
author_facet	Li H Wang P Tang L Sun J Zhang Y Luo W Luo C Hu Z Yang L
author_sort	Li H
title	Distinct Polarization Dynamics of Microglia and Infiltrating Macrophages: A Novel Mechanism of Spinal Cord Ischemia/Reperfusion Injury
title_short	Distinct Polarization Dynamics of Microglia and Infiltrating Macrophages: A Novel Mechanism of Spinal Cord Ischemia/Reperfusion Injury
title_full	Distinct Polarization Dynamics of Microglia and Infiltrating Macrophages: A Novel Mechanism of Spinal Cord Ischemia/Reperfusion Injury
title_fullStr	Distinct Polarization Dynamics of Microglia and Infiltrating Macrophages: A Novel Mechanism of Spinal Cord Ischemia/Reperfusion Injury
title_full_unstemmed	Distinct Polarization Dynamics of Microglia and Infiltrating Macrophages: A Novel Mechanism of Spinal Cord Ischemia/Reperfusion Injury
title_sort	distinct polarization dynamics of microglia and infiltrating macrophages: a novel mechanism of spinal cord ischemia/reperfusion injury
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/4a7a1dfd752841e5a5ee4a974af5524a
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Distinct Polarization Dynamics of Microglia and Infiltrating Macrophages: A Novel Mechanism of Spinal Cord Ischemia/Reperfusion Injury

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