Mast cells and eosinophils have a potential profibrogenic role in Crohn disease

Background: Mast cells and eosinophils have an important role in allergic inflammation and probably also in chronic inflammatory diseases resulting in fibrosis, such as Crohn disease where fibrosis is present as strictures. The involvement of mast cells and eosinophils in Crohn disease fibrosis was investigated. Methods: Biopsies from diseased foci were stained for mast cells, eosinophils, anti-collagen type IV and VIII, laminin and alpha-smooth muscle actin (alpha-SMA) (IHC). Fibroblasts outgrown from the biopsies and a normal fetal intestinal fibroblast line were cultured in the presence of the human mast cell line HMC-1, or of human peripheral blood eosinophil (MACS, purity > 98%) sonicates, or of selected mediators. Fibroblast proliferation (H-3-thymidine), collagen synthesis ([H-3]-proline) and collagen gel contraction were evaluated. Results: Mast cells were present in all the biopsies and only faintly positive for extra cellular matrix (ECM) products. Pronounced eosinophilia was detected in only two cases. Mast cell sonicates increased both Crohn disease (alpha-SMA positive) and control fibroblast proliferation, decreased collagen production and increased collagen gel contraction. Eosinophil sonicates increased fibroblast proliferation, gel contraction and collagen production. TNF-alpha decreased collagen production. Histamine, tryptase and chymase had no influence. Conclusions: These in vitro data show that mast cells and eosinophils could be involved in modulating Crohn disease fibrosis by directly influencing intestinal fibroblast properties.