Inflammatory and alternatively activated human macrophages attract vessel-associated stem cells, relying on separate HMGB1- and MMP-9-dependent pathways
Abstract
Inflammatory macrophages recruited at the site of damaged muscles progressively acquire an alternative activation profile. Inflammatory (M1) and alternatively activated (M2) macrophages exert various and even opposite functions. M1 cells amplify tissue damage, and M2 cells dispose of necrotic fibers and deliver survival signals to myogenic precursors, finally supporting healing. A critical step in muscle healing is the recruitment of myogenic stem cells, including vessel-associated stem cells (mesoangioblasts), which have been demonstrated to home to damaged skeletal muscle selectively and preferentially. Little information is available about the signals involved and the role played by infiltrating macrophages. Here, we report that the polarization of macrophages dramatically skews the secretion of high mobility group box 1 (HMGB1), TNF-alpha, vascular endothelial growth factor, and metalloproteinase 9 (MMP-9), molecules involved in the regulation of cell diapedesis and migration. All polarized macrophage populations were strikingly effective at inducing mesoangioblast migration. By means of specific inhibitors, we verified that the recruitment of mesoangioblasts requires the secretion of HMGB1 and TNF-alpha by M1 cells and of MMP-9 by M2 cells. Together, these data demonstrate a feature, unrecognized previously, of macrophages: their ability to attract stem cells, which is conserved throughout their polarization. Moreover, they open the possibility of novel strategies, aimed…
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Initially infiltrating M1 macrophages produce chemokines and cytokines (TNF-α, IL-1β, IL-6) that are chemoattractant and mitogenic for muscle progenitor cells, including Pax7+ satellite cells.
“Briefly, a number of studies have shown that the chemokines and cytokines (TNF-α, IL-1β, IL-6) produced by initially infiltrating M1 macrophages are chemoattractant and mitogenic for muscle progenitor cells, including Pax7+ satellite cells [115–119].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [115]
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- Authors
- Lolmede, K., Campana, L., Vezzoli, M., Bosurgi, L., Tonlorenzi, R., Clementi, E., Bianchi, M. E., Cossu, G., Manfredi, A. A., Brunelli, S., & Rovere-Querini, P.
- Affiliations
- Cancer Immunotherapy and Gene Therapy Program, Clinical Immunology Unit , Milano , Italy
- IRCCS Ospedale San Raffaele (IT)
- University of Milan (IT)
- Vita-Salute San Raffaele University (IT)
- Corresponding author
- Manfredi, Angelo A
- ORCID
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-02-05
- Volume
- 85
- Issue
- 5
- Pages
- 779-787
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2169084330
- Cited by
- 216
- References
- 6
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 9 · 2022: 5 · 2021: 13 · 2020: 16 · 2019: 6 · 2018: 9 · 2017: 18 · 2016: 9 · 2015: 21 · 2014: 25 · 2013: 19 · 2012: 18
- FWCI
- 8.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Associazione Italiana per la Ricerca sul Cancro
- Ministero della Salute
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Keywords
- macrophage polarization, M1/M2 macrophages, HMGB1, MMP-9, TNF-α, mesoangioblasts, stem cell recruitment, muscle healing, skeletal muscle regeneration, cell migration, vascular endothelial growth factor
- MeSH terms
- Cell Movement, Cells, Cultured, Chemotaxis, Humans, Inflammation, Macrophage Activation, Macrophages, Stem Cells, Tumor Necrosis Factor-alpha, Muscle, Skeletal, Matrix Metalloproteinase 9, HMGB1 Protein, Vascular Endothelial Growth Factor A
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