Alternative activation of macrophages in human peritoneum: implications for peritoneal fibrosis
Abstract
BACKGROUND: Depending on the cytokine microenvironment, macrophages (Mϕ) can adopt a proinflammatory (M1) or a profibrotic (M2) phenotype characterized by the expression of cell surface proteins such as CD206 and CD163 and soluble factors such as CC chemokine ligand 18 (CCL18). A key role for Mϕ in fibrosis has been observed in diverse organ settings. We studied the Mϕ population in a human model of peritoneal dialysis in which continuous stress due to dialysis fluids and recurrent peritonitis represent a risk for peritoneal membrane dysfunction reflected as ultrafiltration failure (UFF) and peritoneal fibrosis. METHODS: We used flow cytometry and quantitative reverse transcription-polymerase chain reaction to analyse the phenotype of peritoneal effluent Mϕ and tested their ability to stimulate the proliferation of human fibroblasts. Mϕ from non-infected patients were compared with those from patients with active peritonitis. Cytokine production was evaluated by enzyme-linked immunosorbent assay (ELISA) in spent dialysates and cell culture supernatants. RESULTS: CD206(+) and CD163(+) M2 were found within peritoneal effluents by flow cytometry analysis, with increased frequencies of CD163(+) cells during peritonitis (P = 0.003). TGFB1, MMP9 and CCL18 messenger RNA (mRNA) levels in peritoneal macrophages (pMϕ) were similar to those found in M2 cells differentiated in vitro. The ability of pMϕ to stimulate fibroblast proliferation correlated with CCL18 mRNA levels (r = 0.924, P = 0.016). CCL18 production by pMϕ was confirmed by immunostaining of cytospin samples and ELISA. Moreover, CCL18 effluent concentrations correlated with decreased peritoneal function, which was evaluated as dialysate to plasma ratio of creatinine (r = 0.724, P < 0.0001), and were significantly higher in patients with UFF (P = 0.0025) and in those who later developed sclerosing peritonitis (P = 0.024). CONCLUSIONS: M2 may participate in human peritoneal fibrosis through the stimulation of fibroblast cell growth and CCL18 production as high concentrations of CCL18 are associated with functional deficiency and fibrosis of the peritoneal membrane.
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In freshly isolated human peritoneal Mp, cell-surface expression of CD206 or the M2c marker CD163 does not correlate with expression of the M2-associated genes TGF-β, CCL18, or matrix metalloproteinase 9.
“Additionally, in freshly isolated human peritoneal Mp, cell-surface expression of CD206 or the M2c marker CD163 does not correlate with expression of the M2-associated genes TGF-, CCL18, or matrix metalloproteinase 9 [53].”
From Macrophage phenotypes during tissue repair (2013) · cites this paper as [53]
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Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms
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- Authors
- Bellón, T., Martínez, V., Lucendo, B., del Peso, G., Castro, M. J., Aroeira, L. S., Rodríguez-Sanz, A., Ossorio, M., Sánchez-Villanueva, R., Selgas, R., & Bajo, M. A.
- Affiliations
- Hospital Universitario La Paz (ES)
- ORCID
- Venue
- Nephrology Dialysis Transplantation
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-02-15
- Volume
- 26
- Issue
- 9
- Pages
- 2995-3005
- ISSN
- 0931-0509 (ISSN-L)
- 1460-2385
- OpenAlex
- W2119628379
- Cited by
- 114
- References
- 54
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 9 · 2023: 6 · 2022: 7 · 2021: 11 · 2020: 9 · 2019: 11 · 2018: 10 · 2017: 7 · 2016: 3 · 2015: 8 · 2014: 7 · 2013: 9 · 2012: 8
- FWCI
- 6.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nephrology Dialysis Transplantation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- alternative macrophage activation, M2 macrophages, peritoneal fibrosis, peritoneal dialysis, peritonitis, CCL18, CD206, CD163, macrophage phenotype, fibroblast proliferation, ultrafiltration failure, sclerosing peritonitis, peritoneal membrane dysfunction, TGF-β1, MMP-9
- MeSH terms
- Adult, Aged, Aged, 80 and over, Enzyme-Linked Immunosorbent Assay, Female, Fibroblasts, Flow Cytometry, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Macrophage Activation, Male, Middle Aged, Peritoneal Dialysis, Peritoneum, Peritonitis, Prognosis, RNA, Messenger, Cytokines, Macrophages, Peritoneal, Chemokines, CC, Cell Proliferation, Young Adult, Peritoneal Fibrosis, Real-Time Polymerase Chain Reaction
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