Giovanna Farro 1 , Michelle Stakenborg 1 , Pedro J Gomez-Pinilla 1 , Evelien Labeeuw 1 , Gera Goverse 1 , Martina Di Giovangiulio 1 , Nathalie Stakenborg 1 , Elisa Meroni 1 , Francesca D'Errico 1 , Yvon Elkrim 2,3 , Damya Laoui 2,3 , Zofia M Lisowski 4 , Kristin A Sauter 4 , David A Hume 4 , Jo A Van Ginderachter 2,3 , Guy E Boeckxstaens 1 , Gianluca Matteoli 1 Show Affiliations »
Abstract
OBJECTIVE: Postoperative ileus (POI) is assumed to result from myeloid cells infiltrating the intestinal muscularis externa (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. DESIGN: IM was performed in mice with defective monocyte migration to tissues (C-C motif chemokine receptor 2, Ccr2-/ - mice) and wild-type (WT) mice to study the role of monocytes and monocyte-derived macrophages (MΦs) during onset and resolution of ME inflammation. RESULTS: At early time points, IM-induced GI transit delay and inflammation were equal in WT and Ccr2 -/- mice. However, GI transit recovery after IM was significantly delayed in Ccr2 -/- 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 Ccr2 -/- mice. CONCLUSION: 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. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
OBJECTIVE: Postoperative ileus (POI) is assumed to result from myeloid cells infiltrating the intestinal muscularis externa (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 . DESIGN: IM was performed in mice with defective monocyte migration to tissues (C-C motif chemokine receptor 2, Ccr2 -/ - mice ) and wild-type (WT) mice to study the role of monocytes and monocyte-derived macrophages (MΦs) during onset and resolution of ME inflammation . RESULTS: At early time points, IM-induced GI transit delay and inflammation were equal in WT and Ccr2 -/- mice . However, GI transit recovery after IM was significantly delayed in Ccr2 -/- 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 Ccr2 -/- mice . CONCLUSION: 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. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Entities: Disease
Gene
Species
Keywords:
colony-stimulating factor 1.; monocyte-derived macrophages; monocytes; postoperative ileus
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Year: 2017
PMID： 28615302 DOI： 10.1136/gutjnl-2016-313144
Source DB: PubMed Journal: Gut ISSN： 0017-5749 Impact factor: 23.059