PT  - JOURNAL ARTICLE
AU  - Giovanna Farro
AU  - Michelle Stakenborg
AU  - Pedro J Gomez-Pinilla
AU  - Evelien Labeeuw
AU  - Gera Goverse
AU  - Martina Di Giovangiulio
AU  - Nathalie Stakenborg
AU  - Elisa Meroni
AU  - Francesca D’Errico
AU  - Yvon Elkrim
AU  - Damya Laoui
AU  - Zofia M Lisowski
AU  - Kristin A Sauter
AU  - David A Hume
AU  - Jo A Van Ginderachter
AU  - Guy E Boeckxstaens
AU  - Gianluca Matteoli
TI  - CCR2-dependent monocyte-derived macrophages resolve inflammation and restore gut motility in postoperative ileus
AID  - 10.1136/gutjnl-2016-313144
DP  - 2017 Dec 01
TA  - Gut
PG  - 2098--2109
VI  - 66
IP  - 12
4099  - http://gut.bmj.com/content/66/12/2098.short
4100  - http://gut.bmj.com/content/66/12/2098.full
SO  - Gut2017 Dec 01; 66
AB  - 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.