M2 macrophages (CD68+ CD163+)

How can hypoxia and danger signals cause the switch from M1 macrophages to M2 macrophages?

The inhibition of HIF1alfa (e.g., by hypoxia, danger signals) will change the phenotype of the macrophage from a pro-inflammatory M1 phenotype to a pro-reparatory (or alternatively activated) M2 phenotype (2).

Which interleukins are typical for the differentiation of M2 macrophages from M1 macrophages?

Activation of their differentiation from the classic M1 macrophage phenotype is typically mediated by interleukin-4 (IL-4) and interleukin-13 (IL-13) (1). However, the molecular pathways that govern their differentiation have remained incompletely understood (1, 7, 11).

Where do M2 macrophages get their energy?

In M2 macrophages (CD68+ CD163+) the tricarboxylic acid (TCA) cycle is intact and participates in oxidative phosphorylation, providing ATP for energy (2, 3). This allows the generation of UDP-GlcNAc intermediates that are necessary for the glycosylation of M2-associated receptors, such as the mannose receptor (3).

How is the M2 macrophage type characterized?

The M2 type is characterized by expression of arginase-1, YM-1, Fizz-1, mannose receptors , scavenger receptors and chemokine genes, such as ccl1 gene , ccl17 gene , ccl22 gene , ccl16 gene , ccl18 gene and ccl24 gene (5). M2 macrophages are typically anti-inflammatory or inflammation-resolving

Are CD68+ and CD163+ the phenotypic markers of M2 macrophages?

Yes, phenotypic markers: are CD68+, CD163+ (7, 8, 9, 10).

What are M2-like genes?

M2-like genes are arg1 gene, cd163 gene, MRC1, and vegfa gene (4).

What factors can trigger the M2 phenotype?

M2 phenotype is triggered by CD4+ Th2 Cells & Cytokines such as interleukin-4 and interleukin-13 as well as anti-inflammatory cytokines , Interleukin-10 (IL-10) and Transforming growth factor beta (TGF-beta), or glucocorticoids (6, 7).

Are Signal transducer and activator of transcription 3 (STAT3), Cyclic AMP-dependent transcription factor ATF-3 (ATF3), Glucocorticoid receptor (GR) transcription factors of M2 macrophages?

Yes, the transcription factors are Signal transducer and activator of transcription 3 (STAT3), Cyclic AMP-dependent transcription factor ATF-3 (ATF3), Glucocorticoid receptor (GR) (7, 8, 9, 10).

What is the relationship between interleukin-4, interleukin-13, and M2 macrophages?

Interleukin-4, and Interleukin-13 are inducing stimuli of M2 macrophages (7, 8, 9, 10)

What are secreted factors of M2 macrophages?

Secreted factors are Interleukin-10, Arginase, TGF beta (7, 8, 9, 10)

References

(1) Byers & Holtzman 2011 Chest 140(3): 768-774
(2) O’Neill et al. 2016
(3) Jha et al. 2015 Immunity 42: 419-430
(4) Azizi et al. 2018 Cell 174(5): 1293–1308
(5) Mantovani et al. 2004 Trends Immunol. 25: 677-686
(6) Hoppstädter et al., 2015
(7) Belizario et al. 2018
(8) Murray et al. 2014 Immunity 41: 14-20
(9) Bashir et al. 2016 Inflamm. Res. 65: 1-11
(10) Wynn & Vannella 2016 Immunity 44(3): 450-462
(11) Faas et al. 2021 Immunity 54: 2531-2546

see also:
Glycolysis & Macrophage polarization
Interleukin-4 (IL-4) & M2 macrophages (CD68+ CD163+)
THP-1 cell line
Tumor-Associated Macrophages (TAM)