Open AccessGranulocyte‐macrophage colony‐stimulating factor elicits bone marrow‐derived cells that promote efficient colonic mucosal healing
Author(s) -
Bernasconi Eric,
Favre Laurent,
Maillard Michel H.,
Bachmann Daniel,
Pythoud Catherine,
Bouzourene Hanifa,
Croze Ed,
Velichko Sharlene,
Parkinson John,
Michetti Pierre,
Velin Dominique
Publication year - 2010
Publication title -
inflammatory bowel diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.932
H-Index - 146
eISSN - 1536-4844
pISSN - 1078-0998
DOI - 10.1002/ibd.21072
Subject(s) - colitis , granulocyte macrophage colony stimulating factor , medicine , bone marrow , myeloid , granulocyte colony stimulating factor , immunology , colony stimulating factor , inflammatory bowel disease , granulocyte , cancer research , cytokine , haematopoiesis , pathology , stem cell , biology , chemotherapy , disease , genetics
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 2010;)