The chemokine CCL18 causes maturation of cultured monocytes to macrophages in the M2 spectrum

Schraufstatter, Ingrid U.; Zhao, Ming; Khaldoyanidi, Sophia K.; DiScipio, Richard G.

doi:10.1111/j.1365-2567.2011.03541.x

Cited by 144Immune cells in cancerChemokine receptors and signalingPhagocytosis and Immune Regulation

The chemokine CCL18 causes maturation of cultured monocytes to macrophages in the M2 spectrum

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Schraufstatter, Ingrid U., Zhao, Ming, Khaldoyanidi, Sophia K., DiScipio, Richard G.·2012·Immunology

DOI 10.1111/j.1365-2567.2011.03541.xPMC PMC3372745

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Abstract

Summary: The observation that human monocytes cultured in the presence of the chemokine CCL18 showed increased survival, led us to profile cytokine expression in CCL18‐stimulated versus control cultures. CCL18 caused significantly increased expression of chemokines (CXCL8, CCL2, CCL3 and CCL22), interleukin‐10 (IL‐10) and platelet‐derived growth factor, but no up‐regulation of M1 cytokines IL‐1β or IL‐12. CCL18‐stimulated monocytes matured into cells with morphological resemblance to IL‐4‐stimulated macrophages, and expressed the monocyte marker CD14 as well the M2 macrophage markers CD206 and 15‐lipoxygenase, but no mature dendritic cell markers (CD80, CD83 or CD86). Functionally, CCL18‐stimulated macrophages showed a high capacity for unspecific phagocytosis and for pinocytosis, which was not associated with an oxidative burst. These findings suggest that CCL18‐activated macrophages stand at the cross‐roads between inflammation and its resolution. The chemokines that are produced in response to CCL18 are angiogenic and attract various leucocyte populations, which sustain inflammation. However, the capacity of these cells to remove cellular debris without causing oxidative damage and the production of the anti‐inflammatory IL‐10 will initiate termination of the inflammatory response. In summary, CCL18 induces an M2 spectrum macrophage phenotype in the absence of IL‐4.

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Multiple pathways induce M2 and M2-like macrophages, including IL-4/IL-13-dependent signaling, TLR and IL-1R signaling with adenosine A(2A)R, CCL18, and CX3CL1.
“Recent studies suggest multiple pathways by which macrophages are induced to develop into M2 and M2-like macrophages. One pathway occurs through an IL-4/IL-13–dependent signaling cascade,95 a second is mediated through TLR and IL-1R signaling and adenosine-sensing receptor A(2A)R,56,95,96 a third is mediated by CCL18,97 and a fourth involves CX3CL1 (fractalkine).57”
From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [97]

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Authors: Schraufstatter, I. U., Zhao, M., Khaldoyanidi, S. K., & DiScipio, R. G.
Affiliations: Sanford Burnham Prebys Medical Discovery Institute (US)
Torrey Pines Institute For Molecular Studies (US)
ORCID: Zhao, Ming
Venue: Immunology
Publisher: Wiley
Published: 2012-03-02
Volume: 135
Issue: 4
Pages: 287-298
ISSN: 0019-2805 (ISSN-L)
1365-2567
DOI: 10.1111/j.1365-2567.2011.03541.x
PMC: PMC3372745
OpenAlex: W1602916344
Cited by: 144
References: 65
Citations by year: 2026: 7 · 2025: 11 · 2024: 14 · 2023: 16 · 2022: 12 · 2021: 17 · 2020: 15 · 2019: 8 · 2018: 7 · 2017: 7 · 2016: 1 · 2015: 6 · 2014: 6 · 2013: 13 · 2012: 4
FWCI: 3.26
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Immunology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Tobacco-Related Disease Research Program
National Institutes of Health
U.S. Public Health Service (R21094878)
National Institute of Diabetes and Digestive and Kidney Diseases (R21DK067084)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Keywords: CCL18, M2 macrophages, monocyte differentiation, macrophage polarization, chemokines, IL-10, CD206, 15-lipoxygenase, phagocytosis, pinocytosis, inflammation resolution, CD14
MeSH terms: Animals, Cell Differentiation, Cells, Cultured, Guinea Pigs, Humans, Macrophages, Monocytes, Phagocytosis, Interleukin-10, Chemokines, Chemokines, CC, Mice

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The chemokine CCL18 causes maturation of cultured monocytes to macrophages in the M2 spectrum

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