Mast Cell and Fibroblast Functional Activity Are Affected by Immunocompetent Cells in Chronic Grafts-vs.-Host Disease.

Abstract

Mast cells (MC)-fibroblast interactions may have a role in chronic inflammation and fibrotic processes. Chronic graft-vs.-host disease (cGVHD) is an autoimmune-like process mediated by immunocompetent T cells resulting in sclerodermoid, fibrotic skin lesions. We assessed the interactions between MC, fibroblasts and immunocompetent cells in a murine model of cGVHD and in cGVHD patiens. We found that mice cGVHD fibroblasts, which have enhanced proliferative potential and produce increased levels of PGE2 and decreased levels of IL-1, maintain rat peritoneal MC and induce maturation of mouse bone marrow-derived MC (BMMC). Moreover, we observed a decreased number of MC and their increased activation both in mice and humans with cGVHD. Murine splenocyte supernatants and human peripheral blood mononuclear cells (PBMC) supernatants caused histamine release from rat peritoneal MC cocultured with 3T3 fibroblasts. In addition, these supernatants increased PGE2 production and decreased proliferation of 3T3 fibroblasts both in the presence and absence of cocultured MC. In conclusion, we have demonstrated the existence of complex interactions between immunocompetent cells, MC and fibroblasts, which may have a role in the inflammatory and fibrotic processes that take place in cGVHD.