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Angiogenesis
Published in: Angiogenesis 1/2014

01-01-2014 | Original Paper

Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo

Authors: Nadine Jetten, Sanne Verbruggen, Marion J. Gijbels, Mark J. Post, Menno P. J. De Winther, Marjo M. P. C. Donners

Published in: Angiogenesis | Issue 1/2014

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Abstract

Objective

Macrophages show extreme heterogeneity and different subsets have been characterized by their activation route and their function. For instance, macrophage subsets are distinct by acting differently under pathophysiological conditions such as inflammation and cancer. Macrophages also contribute to angiogenesis, but the role of various specific subsets in angiogenesis has not been thoroughly investigated.

Methods and results

Matrigel supplemented with macrophage subsets [induced by IFNγ (M1), IL-4 (M2a) or IL-10 (M2c)] was injected subcutaneously in C57BL/6 J mice and analyzed by CD31 staining after 14 days. Increased numbers of endothelial cells and tubular structures were observed in M2-enriched plugs compared to control and other subsets. Additionally, more tubular structures formed in vitro in the presence of M2 macrophages or their conditioned medium. To identify a mechanism for the pro-angiogenic effect, gene expression of angiogenic growth factors was analyzed. Induced expression of basic fibroblast growth factor (Fgf2), insulin-like growth factor-1 (Igf1), chemokine (C–C motif) ligand 2 (Ccl2) and placental growth factor (Pgf) was observed in M2 macrophages. Using a blocking antibody of PlGF to inhibit M2c induced angiogenesis resulted in mildly reduced (40 %) tube formation whereas neutralization of FGF-2 (M2a) signaling by sFGFR1-IIIc affected tube formation by nearly 75 %.

Conclusions

These results indicate that macrophages polarized towards an M2 phenotype have a higher angiogenic potential compared to other subsets. Furthermore, we propose FGF signaling for M2a- and PlGF signaling for M2c-induced angiogenesis as possible working mechanisms, yet, further research should elucidate the exact mechanism for M2-induced angiogenesis.
Appendix
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Metadata
Title
Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo
Authors
Nadine Jetten
Sanne Verbruggen
Marion J. Gijbels
Mark J. Post
Menno P. J. De Winther
Marjo M. P. C. Donners
Publication date
01-01-2014
Publisher
Springer Netherlands
Published in
Angiogenesis / Issue 1/2014
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-013-9381-6

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