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Orekhov et al. Vessel Plus 2019;3:10 Vessel Plus
DOI: 10.20517/2574-1209.2019.04

Review Open Access

Monocyte differentiation and macrophage
polarization

Alexander N. Orekhov 1,2,3 , Varvara A. Orekhova , Nikita G. Nikiforov , Veronika A. Myasoedova , Andrey V.
1
1
1
Grechko , Elena B. Romanenko , Dongwei Zhang , Dimitry A. Chistiakov 7
6
5
4
1 Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow 125315, Russia.
2 Centre of Collective Usage, Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia.
3 Institute for Atherosclerosis Research, Skolkovo Innovative Center, Moscow 121609, Russia.
4 Federal Scientific Clinical Center for Resuscitation and Rehabilitation, Moscow 109240, Russia.
5 Department of Molecular Basis of Ontogenesis, Belozersky Institute of Physical and Chemical Biology, Moscow State University,
Moscow 119234, Russia.
6 Diabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
7 Department of Neurochemistry, Division of Basic and Applied Neurobiology, Serbsky Federal Medical Research Center of
Psychiatry and Narcology, Moscow 119991, Russia.
Correspondence to: Dr. Alexander N. Orekhov, Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology,
Moscow 125315, Russia. E-mail: a.h.opexob@gmail.com

How to cite this article: Orekhov AN, Orekhova VA, Nikiforov NG, Myasoedova VA, Grechko AV, Romanenko EB, Zhang D,
Chistiakov DA. Monocyte differentiation and macrophage polarization. Vessel Plus 2019;3:10.
http://dx.doi.org/10.20517/2574-1209.2019.04

Received: 25 Jan 2019 First Decision: 5 Feb 2019 Revised: 10 Feb 2019 Accepted: 11 Feb 2019 Published: 22 Mar 2019
Science Editor: Alexander N. Orekhov Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Circulating monocytes are recruited to tissues, where they differentiate to macrophages and take part in the inflammation
process or tissue remodeling. According to the traditional concept, macrophages are classified into pro-inflammatory
(M1), non-activated (M0) or anti-inflammatory (M2) subsets that play distinct roles in the initiation and resolution of
inflammation. This heterogeneity exists already at the monocyte level since monocytes can also belong to pro- or anti-
inflammatory phenotypes. Growth factors, such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and
M-CSF play a principal role in their activation: GM-CSF drives the differentiation of “pro-inflammatory” monocytes to M1
macrophages, while M-CSF regulates differentiation of the “anti-inflammatory” subset of monocytes to M0 macrophages
that have M2-like phenotypic and functional properties. More recent experimental findings led to a substantial update
of monocyte-macrophage nomenclature to include the nature of the polarizing signal. In response to pro-inflammatory
stimuli, monocytes can be directly polarized into 3 subsets of macrophages with the pro-inflammatory M1-like phenotype;
with macrophages induced by interferon-γ having the strongest pro-inflammatory properties. When exposed to various
anti-inflammatory stimuli, monocytes can differentiate to at least 5 subsets of M2-like macrophages. Of those, a subset
generated under exposure to IL-4 (IL-13) has the most typical M2-like characteristics. Both in humans and in mice,

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
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sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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