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Functional phenotypes of macrophages and the M1-M2 polarization concept. Part I. Proinflammatory phenotype

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Abstract

Current concepts concerning the main functional phenotypes of mononuclear phagocytes are systematized, molecular mechanisms of their formation are considered, and the functional polarization concept of macrophages is critically analyzed. Mechanisms of macrophage priming activation mediated by pattern recognition receptors TLR, NLR, RLR, and CLR are described, and the features of each phenotype acquired via various pattern recognition receptors are emphasized. It is concluded that there is a huge variety of proinflammatory phenotypes from highly to poorly polarized ones. Thus the widespread notion of “classical activation” of macrophage concerns just a particular case of proinflammatory phenotype formation.

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Abbreviations

AIM2:

absent in melanoma 2

ASC:

CARD domain containing apoptosis-associated speck-like protein

CARD:

caspase activating and recruiting domain

CLR:

C-type lectin receptors

CTLL:

C-type lectin-like receptors

DAI:

DNA-dependent activator of IFN-regulatory factors

DAMP:

danger/damage-associated molecular patterns

DISC:

death-inducing signaling complex

ERK:

extracellular signal-regulated kinases

FADD:

Fas-associated protein with death domain

HIN200:

hematopoietic IFN-inducible nuclear protein with 200-amino-acid repeat

HMGB1:

high mobility group box 1 protein

IFI16:

γ-interferon-inducible protein 16

IFN:

interferon

IL:

interleukin

iNOS:

inducible NO synthase

IPS1:

stimulator 1 of IFN-β promoter

IRAK1:

IL-1 receptor-associated kinase 1

IRF:

IFN regulatory factor

ISRE:

IFN-stimulated response elements

ITAM:

immunoreceptor tyrosine-based activation motif

JNK:

Jun N-terminal protein kinase

LBP:

LPS-binding protein

LPS:

lipopolysaccharide

LRR:

leucine-rich repeat domain

MAPK:

mitogen-activated protein kinases

MD2:

myeloid differentiation protein-2

MDA5:

melanoma differentiation associated gene 5

Mph:

macrophage

NK:

natural killer

NLR:

nucleotide oligomerization domain (NOD)-like receptors

PAMP:

pathogen-associated molecular patterns

PRR:

pattern recognition receptors

RIP1:

receptor-interacting protein 1

RLR:

retinoic acid-inducible gene-I-like receptors

STAT:

signal transducer and transcription activator

STING:

stimulator of interferon genes

TAB1:

TAK1-binding protein

TAK1:

TGF-β activated kinase 1

TGF:

transforming growth factor

TIR:

Toll/IL-1R domain

TIRAP:

Toll receptor IL-1R domain-containing adaptor protein

TLR:

toll-like receptors

TNF:

tumor necrosis factor

TRADD:

TNFR1-associated death domain

TRAF:

TNF-receptor-associated factor

TRAM:

TRIFrelated adaptor molecule

TRIF:

TIR-domain-containing adaptor-inducing IFN-β

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Authors and Affiliations

  1. Research Institute of Internal Medicine, Siberian Branch of the Russian Academy of Medical Sciences, ul. B. Bogatkova 175/1, 630089, Novosibirsk, Russia

    Y. Sh. Schwartz

  2. Meshalkin Research Institute for Circulation Pathology, ul. Rechkunovskaya 15, 630055, Novosibirsk, Russia

    A. V. Svistelnik

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  1. Y. Sh. Schwartz
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Correspondence to Y. Sh. Schwartz.

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Original Russian Text © Y. Sh. Schwartz, A. V. Svistelnik, 2012, published in Biokhimiya, 2012, Vol. 77, No. 3, pp. 312–329.

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Schwartz, Y.S., Svistelnik, A.V. Functional phenotypes of macrophages and the M1-M2 polarization concept. Part I. Proinflammatory phenotype. Biochemistry Moscow 77, 246–260 (2012). https://doi.org/10.1134/S0006297912030030

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