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

Abstract

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.

An update on equine post‐operative ileus: Definitions, pathophysiology and management

“…IL-10 knockout mice fail to resolve their muscularis inflammatory response compared with wild-type mice, resulting in high mortality rates [72]. The administration of macrophage colony-stimulating factor-1 fusion protein (CSF1-Fc) [73] not only restored monocyte and MM numbers but reduced neutrophil infiltration in the muscularis, increased anti-inflammatory gene expression and improved GIT transit time following IM [55]. Additionally, while the initial leucocytic infiltrate of neutrophils and monocytes to the muscularis has been associated with SM dysfunction leading to POI, the role of monocytes/macrophages in resolution of POI has not been studied, until recently.…”

“…Results derived predominantly from rodent studies have attributed the prolonged phase of POI to inflammation within the intestinal muscularis [37, 54,55]. Accordingly, the experimental induction of POI by IM has been prevented by the inhibition of mast cells [56], macrophages [57] or more general leucocytic infiltration [58,59].…”

Janus-like monocytes regulate postoperative ileus

“…Although both studies conclude that elicited monocytes are critical for the initiation of POI, Farro et al show that these cells have opposite effects during the resolution of POI, when they gradually acquire the features of tissue-protective macrophages 1. Indeed this protective function may be the principal role of elicited monocytes in POI, as monocyte/macrophage depletion leads to enhanced pathology, increased neuronal damage and a delay in recovery.…”

“…These studies show that elicited monocytes are critical for producing NO and initiating POI in both the small intestine and colon, but there are important differences between these tissues in the mechanisms involved. First, resident ME macrophages can also contribute to POI in the small intestine, perhaps being activated directly by products of the local microbiota that have leaked through the mechanically damaged intestinal barrier 1. This does not occur in the colon, where the authors suggest that resident macrophages have been rendered unresponsive by the larger load of microbiota in this site.…”

“…Indeed, Farro et al show that administration of the monocyte-macrophage specific growth factor colony stimulating factor-1 (can promote resolution of experimental POI,1 an approach that has also proved successful in preclinical studies of liver injury 11. For this idea to be realised, it would clearly be important to confirm that the pathogenetic processes outlined in mice extend to humans, something that will require the development of suitable biomarkers that allow POI and monocyte recruitment to be monitored.…”