Dynamic changes of peritoneal macrophages and subpopulations during ulcerative colitis to metastasis of colorectal carcinoma in a mouse model
Dynamic changes of peritoneal macrophages and subpopulations during ulcerative colitis to metastasis of colorectal carcinoma in a mouse model
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小鼠溃疡性结肠炎至结直肠癌转移过程中腹腔巨噬细胞及其亚群的动态变化
DOI：
10.1007/s00011-013-0619-y
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发表时间：
2013-07-01
影响因子：
6.7
通讯作者：
Shen, Shourong
中科院分区：
文献类型：
--
作者：
Wang, Wei;Li, Xiayu;Shen, Shourong
溃疡性结肠炎患者患结直肠癌的风险增加，但关于腹膜巨噬细胞如何参与溃疡性结肠炎相关的致癌作用知之甚少。我们研究了溃疡性结肠炎相关致癌过程中腹膜巨噬细胞以及M1/M2亚群的变化。
我们使用雄性Crj:CD - 1（ICR）小鼠，通过组织病理学、流式细胞术、免疫荧光、酶联免疫吸附测定（ELISA）检测细胞因子表达以及实时定量聚合酶链反应（QRT - PCR），在偶氮甲烷（AOM）和葡聚糖硫酸钠（DSS）诱导的化学性结肠炎相关癌症小鼠模型中，研究了腹膜巨噬细胞以及M1/M2亚群的表达和功能变化。
在组织病理学、流式细胞术、细胞因子检测和基因表达分析中观察到的显著证据都表明，在从炎症性增生到癌症和转移的进展过程中，腹膜M2巨噬细胞诱导的炎症相关细胞因子（白细胞介素 - 1β、白细胞介素 - 10、白细胞介素 - 12、白细胞介素 - 6、肿瘤坏死因子 - α）以及迁移/侵袭相关因子（粒细胞集落刺激因子、粒细胞 - 巨噬细胞集落刺激因子、CXC趋化因子受体4、血管内皮生长因子、转化生长因子 - β、细胞间黏附分子 - 1）显著增加。在M1巨噬细胞发生腹膜转移过程中，出现了类似的功能变化，但极化未改变。
这些结果表明，腹膜M2巨噬细胞在溃疡性结肠炎相关的致癌过程中起着关键作用，包括促炎和抗炎轴失衡以及迁移/侵袭相关因子表达增强。此外，在致癌和转移过程中，M1巨噬细胞发生功能变化但极化未改变。
Objective and designPatients with ulcerative colitis have increased risk of colorectal carcinoma, but little is known about how peritoneal macrophages are involved in ulcerative colitis-associated carcinogenesis. We investigated the alteration of peritoneal macrophages and M1/M2 subpopulations during ulcerative colitis-associated carcinogenesis.Materials and methodsExpression and functional changes in peritoneal macrophages and M1/M2 subpopulations were investigated by histopathology, flow cytometry, immunofluorescence, cytokines expression by ELISA and QRT-PCR in an azoxymethane (AOM)- and dextran sodium sulfate (DSS)-induced chemical colitis-associated carcinoma mouse model using male Crj:CD-1 (ICR) mice.ResultsStriking evidence observed in histopathology, flow cytometry, cytokine detection, and gene expression analysis all revealed that inflammation-associated cytokines (IL-1β, IL-10, IL-12, IL-6, TNF-α) and migration/invasion-associated factors (G-CSF, GM-CSF, CXCR4, VEGF, TGF-β, ICAM-1) induced by peritoneal M2 macrophages increased significantly during the progression from inflammatory hyperplasia to carcinoma and metastasis. Similar functional changes occurred during peritoneal metastasis in M1 macrophages without changed polarization.ConclusionsThese results suggested that peritoneal M2 macrophages played a critical role in ulcerative colitis-associated carcinogenesis, including unbalanced pro-inflammatory and anti-inflammatory axis and enhanced expression of migration/invasion-associated factors. Furthermore, functional changes of M1 macrophages occurred without changed polarization during carcinogenesis and metastasis.