Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
Gut. 2017 Dec;66(12):2098-2109. doi: 10.1136/gutjnl-2016-313144. Epub 2017 Jun 14.
Postoperative ileus (POI) is assumed to result from myeloid cells infiltrating the intestinal (ME) in patients undergoing abdominal surgery. In the current study, we investigated the role of infiltrating monocytes in a murine model of intestinal manipulation (IM)-induced POI in order to clarify whether monocytes mediate tissue damage and intestinal dysfunction or they are rather involved in the recovery of gastrointestinal (GI) motility.
IM was performed in mice with defective monocyte migration to tissues (C-C motif chemokine receptor 2, mice) and wild-type (WT) mice to study the role of monocytes and monocyte-derived macrophages (MΦs) during onset and resolution of ME inflammation.
At early time points, IM-induced GI transit delay and inflammation were equal in WT and mice. However, GI transit recovery after IM was significantly delayed in mice compared with WT mice, associated with increased neutrophil-mediated immunopathology and persistent impaired neuromuscular function. During recovery, monocyte-derived MΦs acquire pro-resolving features that aided in the resolution of inflammation. In line, bone marrow reconstitution and treatment with MΦ colony-stimulating factor 1 enhanced monocyte recruitment and MΦ differentiation and ameliorated GI transit in mice.
Our study reveals a critical role for monocyte-derived MΦs in restoring intestinal homeostasis after surgical trauma. From a therapeutic point of view, our data indicate that inappropriate targeting of monocytes may increase neutrophil-mediated immunopathology and prolong the clinical outcome of POI, while future therapies should be aimed at enhancing MΦ physiological repair functions.
术后肠麻痹（POI）被认为是腹部手术患者肠道中髓样细胞浸润（ME）的结果。在本研究中，我们研究了浸润单核细胞在肠道操作（IM）诱导的 POI 小鼠模型中的作用，以阐明单核细胞是否介导组织损伤和肠道功能障碍，或者它们是否参与胃肠道（GI）运动的恢复。
在组织中单核细胞迁移缺陷的小鼠（C-C 基序趋化因子受体 2 缺陷小鼠， 小鼠）和野生型（WT）小鼠中进行 IM，以研究单核细胞和单核细胞衍生的巨噬细胞（MΦ）在 ME 炎症发生和消退期间的作用。
在早期时间点，WT 小鼠和 小鼠的 IM 诱导的 GI 转运延迟和炎症程度相同。然而，与 WT 小鼠相比， 小鼠的 IM 后 GI 转运恢复明显延迟，与中性粒细胞介导的免疫病理学增加和持续受损的神经肌肉功能相关。在恢复过程中，单核细胞衍生的 MΦ获得了促修复特征，有助于炎症的消退。与此一致，骨髓重建和 MΦ集落刺激因子 1 治疗增强了单核细胞募集和 MΦ分化，并改善了 小鼠的 GI 转运。
我们的研究揭示了单核细胞衍生的 MΦ 在手术创伤后恢复肠道内稳态中的关键作用。从治疗的角度来看，我们的数据表明，对单核细胞的不适当靶向可能会增加中性粒细胞介导的免疫病理学，并延长 POI 的临床结局，而未来的治疗方法应该旨在增强 MΦ 的生理修复功能。
