Suppression of experimental colitis by intestinal mononuclear phagocytes
Suppression of experimental colitis by intestinal mononuclear phagocytes
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DOI：
10.1189/jlb.1205734
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发表时间：
2006-10-01
影响因子：
5.5
通讯作者：
Cohen, Donald A.
中科院分区：
文献类型：
--
作者：
Qualls, Joseph E.;Kaplan, Alan M.;Cohen, Donald A.
先天免疫在炎症性肠病中的作用(1111)仍然是一个非常感兴趣的领域。巨噬细胞(M环分裂)和树突状细胞(DC)被认为是调节IBD发病的重要因素。本研究的目的是确定肠道单核巨噬细胞(IMNP)在葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎中是否起到病理或保护作用。应用有条件的M环分割/DC耗竭转基因小鼠系-M环分割/DC耗尽转基因小鼠--Fas诱导的细胞凋亡-系统去除IMNP，发现M环分割/DC耗竭小鼠的DSS结肠炎组织病理学改变比M环分割/DC完整小鼠更严重。类似地，C57BL/6、BALB/c和CB.17/SCID小鼠通过氯屈膦酸盐脂质体局部清除IMNP也增加了DSS结肠炎的严重程度，表现为与M Circle Divide/DC完整的DSS治疗小鼠相比，组织病理学、体重减轻、直肠出血、粪便稠度和结肠长度降低。组织学显示，在DSS治疗过程中，IMNP耗尽导致中性粒细胞炎症增加，附壁损伤增加，杯状细胞粘蛋白耗竭增加。IMNP耗竭不能进一步增加DSS诱导的肿瘤坏死因子-α和干扰素-γ的表达，但显著增加CXCL1趋化因子的表达。与单用DSS相比，M Circle Divide/DC耗竭组小鼠结肠髓过氧化物酶活性增强，与病变结肠中性粒细胞浸润增加相一致。与单用M环分割/DC耗竭相比，中性粒细胞去除联合M环分割/DC去除可预防DSS结肠炎严重程度的增加。这项研究表明，IMNP在急性结肠炎的发生发展过程中起到保护作用，这种保护作用与M环分割/DC介导的中性粒细胞浸润下调有关。
The contribution of innate immunity to inflammatory bowel disease (1111)) remains an area of intense interest. Macrophages (M circle divide) and dendritic cells (DC) are considered important factors in regulating the onset of IBD. The goal of this study was to determine if intestinal mononuclear phagocytes (iMNP) serve a pathological or protective role in dextran sulfate sodium (DSS)-induced colitis in mice. Using a conditional M circle divide/DC depletion transgenic mouse line-M circle divide Fas-induced apoptosis-to systemically deplete iMNP, DSS colitis histopathology was shown to be more severe in M circle divide/DC-depleted compared with M circle divide/DC-intact mice. Similarly, localized iMNP depletion by clodronate-encapsulated liposomes into C57BL/6, BALB/c, and CB.17/SCID mice also increased DSS colitis severity, as indicated by increased histopathology, weight loss, rectal bleeding, decreased stool consistency, and colon length compared with M circle divide/DC-intact, DSS-treated mice. Histology revealed that iMNP depletion during DSS treatment led to increased neutrophilic inflammation, increased epithetial injury, and enhanced mucin depletion from Goblet cells. iMNP depletion did not further elevate DSS-induced expression of TNF-alpha and IFN-gamma mRNA but significantly increased expression of CXCL1 chemokine mRNA. Myeloperoxidase activity was increased in colons of M circle divide/DC-depleted, DSS-treated mice, compared with DSS alone, coincident with increased neutrophil infiltration in diseased colons. Neutrophil depletion combined with M circle divide/DC depletion prevented the increase in DSS colitis severity compared with M circle divide/DC depletion alone. This study demonstrates that iMNP can serve a protective role during development of acute colitis and that protection is associated with M circle divide/DC-mediated down-regulation of neutrophil infiltration.