CCR2-dependent monocyte-derived macrophages resolve inflammation and restore gut motility in postoperative ileus

Farro, Giovanna, Stakenborg, Michelle, Gomez-Pinilla, Pedro J., Labeeuw, Evelien, Goverse, Gera, Giovangiulio, Martina Di, Stakenborg, Nathalie, Meroni, Elisa, D'Errico, Francesca, Elkrim, Yvon, Laoui, Damya, Lisowski, Zofia M., Sauter, Kristin A., Hume, David A., Van Ginderachter, Jo A., Boeckxstaens, Guy E. and Matteoli, Gianluca (2017) CCR2-dependent monocyte-derived macrophages resolve inflammation and restore gut motility in postoperative ileus. Gut, 66 12: 2098-2109. doi:10.1136/gutjnl-2016-313144


Author Farro, Giovanna
Stakenborg, Michelle
Gomez-Pinilla, Pedro J.
Labeeuw, Evelien
Goverse, Gera
Giovangiulio, Martina Di
Stakenborg, Nathalie
Meroni, Elisa
D'Errico, Francesca
Elkrim, Yvon
Laoui, Damya
Lisowski, Zofia M.
Sauter, Kristin A.
Hume, David A.
Van Ginderachter, Jo A.
Boeckxstaens, Guy E.
Matteoli, Gianluca
Title CCR2-dependent monocyte-derived macrophages resolve inflammation and restore gut motility in postoperative ileus
Journal name Gut   Check publisher's open access policy
ISSN 1468-3288
0017-5749
Publication date 2017-12-01
Sub-type Article (original research)
DOI 10.1136/gutjnl-2016-313144
Open Access Status Not yet assessed
Volume 66
Issue 12
Start page 2098
End page 2109
Total pages 12
Place of publication London, United Kingdom
Publisher BMJ Publishing Group
Language eng
Formatted 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.
Keyword Colony-stimulating factor 1
Monocyte-derived macrophages
Monocytes
Postoperative ileus
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
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Created: Fri, 20 Apr 2018, 09:30:27 EST