Neuroinflammation and M2 microglia: the good, the bad, and the inflamed

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

The concept of multiple macrophage activation states is not new. However, extending this idea to resident tissue macrophages, like microglia, has gained increased interest in recent years. Unfortunately, the research on peripheral macrophage polarization does not necessarily translate accurately to their central nervous system (CNS) counterparts. Even though pro- and anti-inflammatory cytokines can polarize microglia to distinct activation states, the specific functions of these states is still an area of intense debate. This review examines the multiple possible activation states microglia can be polarized to. This is followed by a detailed description of microglial polarization and the functional relevance of this process in both acute and chronic CNS disease models described in the literature. Particular attention is given to utilizing M2 microglial polarization as a potential therapeutic option in treating diseases.

Related collections

Most cited references 105

Record: found
Abstract: found
Article: not found

Nitric oxide and macrophage function.

John MacMicking, Qiao-wen Xie, Carl Nathan (1997)

At the interface between the innate and adaptive immune systems lies the high-output isoform of nitric oxide synthase (NOS2 or iNOS). This remarkable molecular machine requires at least 17 binding reactions to assemble a functional dimer. Sustained catalysis results from the ability of NOS2 to attach calmodulin without dependence on elevated Ca2+. Expression of NOS2 in macrophages is controlled by cytokines and microbial products, primarily by transcriptional induction. NOS2 has been documented in macrophages from human, horse, cow, goat, sheep, rat, mouse, and chicken. Human NOS2 is most readily observed in monocytes or macrophages from patients with infectious or inflammatory diseases. Sustained production of NO endows macrophages with cytostatic or cytotoxic activity against viruses, bacteria, fungi, protozoa, helminths, and tumor cells. The antimicrobial and cytotoxic actions of NO are enhanced by other macrophage products such as acid, glutathione, cysteine, hydrogen peroxide, or superoxide. Although the high-output NO pathway probably evolved to protect the host from infection, suppressive effects on lymphocyte proliferation and damage to other normal host cells confer upon NOS2 the same protective/destructive duality inherent in every other major component of the immune response.

0 comments Cited 655 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Inflammation and Alzheimer's disease.

H Akiyama, S. Barger, S Barnum … (2000)

Inflammation clearly occurs in pathologically vulnerable regions of the Alzheimer's disease (AD) brain, and it does so with the full complexity of local peripheral inflammatory responses. In the periphery, degenerating tissue and the deposition of highly insoluble abnormal materials are classical stimulants of inflammation. Likewise, in the AD brain damaged neurons and neurites and highly insoluble amyloid beta peptide deposits and neurofibrillary tangles provide obvious stimuli for inflammation. Because these stimuli are discrete, microlocalized, and present from early preclinical to terminal stages of AD, local upregulation of complement, cytokines, acute phase reactants, and other inflammatory mediators is also discrete, microlocalized, and chronic. Cumulated over many years, direct and bystander damage from AD inflammatory mechanisms is likely to significantly exacerbate the very pathogenic processes that gave rise to it. Thus, animal models and clinical studies, although still in their infancy, strongly suggest that AD inflammation significantly contributes to AD pathogenesis. By better understanding AD inflammatory and immunoregulatory processes, it should be possible to develop anti-inflammatory approaches that may not cure AD but will likely help slow the progression or delay the onset of this devastating disorder.

0 comments Cited 623 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models.

Paige E. Cramer, John R Cirrito, Daniel Wesson … (2012)

Alzheimer's disease (AD) is associated with impaired clearance of β-amyloid (Aβ) from the brain, a process normally facilitated by apolipoprotein E (apoE). ApoE expression is transcriptionally induced through the action of the nuclear receptors peroxisome proliferator-activated receptor gamma and liver X receptors in coordination with retinoid X receptors (RXRs). Oral administration of the RXR agonist bexarotene to a mouse model of AD resulted in enhanced clearance of soluble Aβ within hours in an apoE-dependent manner. Aβ plaque area was reduced more than 50% within just 72 hours. Furthermore, bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function. Thus, RXR activation stimulates physiological Aβ clearance mechanisms, resulting in the rapid reversal of a broad range of Aβ-induced deficits.

0 comments Cited 349 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Jonathan D Cherry

John A Olschowka

M Kerry O’Banion

Journal

Journal ID (nlm-ta): J Neuroinflammation

Journal ID (iso-abbrev): J Neuroinflammation

Title: Journal of Neuroinflammation

Publisher: BioMed Central

ISSN (Electronic): 1742-2094

Publication date Collection: 2014

Publication date (Electronic): 3 June 2014

Volume: 11

Page: 98

Affiliations

[1 ]Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA

[2 ]Department of Neurobiology & Anatomy, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA

Article

Publisher ID: 1742-2094-11-98

DOI: 10.1186/1742-2094-11-98

PMC ID: 4060849

PubMed ID: 24889886

SO-VID: 7a0712c7-8bab-48ce-885a-e3b228d37c6d

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Neuroinflammation and M2 microglia: the good, the bad, and the inflamed

Read this article at

Abstract

Related collections

Good practices in (cog-neuro) science and science communication

Most cited references 105

Nitric oxide and macrophage function.

Inflammation and Alzheimer's disease.

ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models.

Author and article information

Contributors

Journal

Affiliations

Article

History

Categories

Comments

Comment on this article

Similar content 26

Cited by 629

Most referenced authors 2,557