GM-CSF stimulates colonic repair

[Kofi]

Inflamm Bowel Dis. 2009 Jul 28;
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Granulocyte-macrophage colony-stimulating factor elicits bone
marrow-derived cells that promote efficient colonic mucosal healing.
Bernasconi E, Favre L, Maillard MH, Bachmann D, Pythoud C, Bouzourene H,
Croze E, Velichko S, Parkinson J, Michetti P, Velin D.
Division of Gastroenterology and Hepatology, Centre Hospitalier
Universitaire Vaudois and University of Lausanne, Switzerland.

BACKGROUND:: Granulocyte-macrophage colony-stimulating factor (GM-CSF)
therapy is effective in treating some Crohn's disease (CD) patients and
protects mice from colitis induced by dextran sulfate sodium (DSS)
administration. However, its mechanisms of action remain elusive. We
hypothesized that GM-CSF affects intestinal mucosal repair. METHODS::
DSS colitic mice were treated with daily pegylated GM-CSF or saline and
clinical, histological, and inflammatory parameters were kinetically
evaluated. Further, the role of bone marrow-derived cells in the impact
of GM-CSF therapy on DSS colitis was addressed using cell transfers.
RESULTS:: GM-CSF therapy reduced clinical signs of colitis and the
release of inflammatory mediators. GM-CSF therapy improved mucosal
repair, with faster ulcer reepithelialization, accelerated
hyperproliferative response of epithelial cells in ulcer-adjacent
crypts, and lower colonoscopic ulceration scores in GM-CSF-administered
mice relative to untreated mice. We observed that GM-CSF-induced
promotion of mucosal repair is timely associated with a reduction in
neutrophil numbers and increased accumulation of CD11b(+) monocytic
cells in colon tissues. Importantly, transfer of splenic GM-CSF-induced
CD11b(+) myeloid cells into DSS-exposed mice improved colitis, and
lethally irradiated GM-CSF receptor-deficient mice reconstituted with
wildtype bone marrow cells were protected from DSS-induced colitis upon
GM-CSF therapy. Lastly, GM-CSF-induced CD11b(+) myeloid cells were shown
to promote in vitro wound repair. CONCLUSIONS:: Our study shows that
GM-CSF-dependent stimulation of bone marrow-derived cells during
DSS-induced colitis accelerates colonic tissue repair. These data
provide a putative mechanism for the observed beneficial effects of
GM-CSF therapy in Crohn's disease. (Inflamm Bowel Dis 2009;).
PMID: 19639560