Effect of coculture of rodent mast cells with murine chronic graft-versus-host disease (cGVHD)-derived fibroblasts.

We investigated whether murine chronic graft-versus-host disease (cGVHD)-derived skin fibroblasts maintain the viability and functional activity of rat peritoneal connective tissue-mast cells (CTMCs) and whether they affect the change in phenotype of mouse bone marrow-derived mast cells (BMMCs). Skin fibroblasts were isolated before the development of fibrosis (day 5), during overt fibrosis (day 28), and after recovery from fibrosis (day 120). cGVHD fibroblasts of days 5 and 28 exhibited enhanced proliferation, a property that was maintained through several subcultures. CTMCs adhered to the same extent, did not divide, and maintained their viability in all the different cultures. When CTMCs were activated with compound 48/80, they released approximately 80% of their histamine content, indicating that coculture with cGVHD fibroblasts did not adversely affect CTMC function. The amount of histamine found in the medium of 8 days CTMC/cGVHD fibroblast coculture was similar to that found in control culture. These findings suggest that the degranulation of dermal MCs, characteristic of cGVHD, is not due to a direct activating effect of the cGVHD fibroblasts on the MCs. BMMCs seeded on cGVHD fibroblasts acquired the capacity for safranin staining and increased their histamine content, indicative of a change to CTMCs. Thus, cGVHD fibroblasts are able to provide a microenvironment adequate for maintaining viability and activity of CTMCs and for promoting maturation and change in phenotype of BMMCs.