High glucose contributes to the polarization of peritoneal macrophages to the M2 phenotype in vivo and in vitro

Lin,Jieshan; Kong,Qingyu; Hao,Wenke; Hu,Wenxue

doi:10.3892/mmr.2020.11130

High glucose contributes to the polarization of peritoneal macrophages to the M2 phenotype in vivo and in vitro

Authors:
- Jieshan Lin
- Qingyu Kong
- Wenke Hao
- Wenxue Hu
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Affiliations: Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, Guangdong 510080, P.R. China, Department of Nephrology, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China
Published online on: May 5, 2020 https://doi.org/10.3892/mmr.2020.11130
Pages: 127-134
Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glucose is the primary osmotic medium used in most peritoneal dialysis (PD) solutions, and long‑term exposure to high glucose is a major contributor to peritoneal fibrosis. Our previous study revealed that M2 macrophages participate in the development of PD‑related fibrosis in a rat model. In the present study, the effects of high glucose on peritoneal macrophage polarization in vivo and in vitro were further evaluated. Continuous ambulatory PD (CAPD) patients with an overnight dwell of 1.5 or 2.5% glucose dialysate were recruited for this study. Overnight effluent samples from patients with CAPD (2,000 ml) were centrifuged to collect cells from the peritoneal cavity. J774A.1 cells (murine macrophages from ascites) were cultured in different concentrations of glucose. Macrophage phenotype markers were detected by flow cytometry. The levels of cytokines in PD effluent and the supernatant of murine macrophages were detected by enzyme‑linked immunosorbent assays. The activity of arginase was determined by quantitative colorimetric analysis. In total, 107 CAPD subjects (92 patients using 1.5% glucose dialysate and 15 patients using 2.5% glucose dialysate) were recruited. The percentage of M1 macrophages (CD14‑ and CCr7‑positive cells) in the 1.5 and 2.5% glucose dialysate groups was 23.0±13.3 and 24.9±12.0%, respectively. The difference was not significant (P>0.05). The percentage of M2 macrophages (CD14‑ and CD206‑positive cells) in the 1.5% glucose dialysate group (36.2±11.4%) was significantly decreased compared to the 2.5% glucose dialysate group (43.2±7.4%) (P<0.05). Murine macrophages were cultured in a high‑glucose in vitro environment, and the percentage of M1 macrophages in 138.8 mmol/l glucose medium significantly increased over time. The percentage of M2 macrophages increased in a glucose concentration‑dependent and time‑dependent manner. Arginase 1 in murine macrophages and the level of transforming growth factor β1 in the supernatant increased in a glucose concentration‑dependent manner. In conclusion, high glucose contributed to the polarization of peritoneal macrophages to the M2 phenotype, which may play an important role in the pathogenesis of PD‑related fibrosis.

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