Increased numbers of microchimeric cells of fetal origin are associated with dermal fibrosis in mice following injection of vinyl chloride

Objective, To develop a murine model for use in examining the role of micro chimeric cells and certain chemical exposures in the pathogenesis of system ic sclerosis (SSc), Methods. Female BALB/cJ retired breeder mice were bled before and after vin yl chloride injection. The DNA from their white blood cells was obtained, a nd the number of microchimeric cell equivalents was determined by quantitat ive polymerase chain reaction using DNA primers specific for the H-2K(b) ge ne, a sequence not found in SALB/cJ mice. Skin was obtained at autopsy, emb edded in paraffin, sectioned, and stained with Masson's trichrome, Hydroxyp roline analyses were performed on 4-mm skin biopsy samples. Results. Microchimeric cells were identified and quantitated before and aft er 20 daily intraperitoneal injections of vinyl chloride. The number of mic rochimeric cells in the peripheral blood increased an average of 48-fold af ter treatment with vinyl chloride. Histologic examination of the skin of th ese same mice (which had an increased number of microchimeric cells) showed inflammation, with abundant fibroblasts and a heavy mononuclear infiltrati on in the dermis, The collagen fibers appeared densely packed and disorgani zed. Histologic examination of the skin of untreated retired breeder mice a nd treated virgin mice appeared normal. Quantitative assays to determine th e collagen content of skin biopsy samples obtained from treated microchimer ic mice compared with nontreated microchimeric or with treated nonmicrochim eric mice showed a 2-3-fold increase in collagen content in the treated mic rochimeric mice. Extraordinary splenomegaly was present in the vinyl chlori de-treated microchimeric mice, accompanied by cellular infiltration and fib rosis, Conclusion. The results suggest that vinyl chloride injections into BALB/cJ retired breeder mice lead to activation of microchimeric cells, which caus es the cells to divide and multiply. The correlation between the 48-fold in crease in microchimeric cells and the appearance of dermal inflammation and fibrosis similar to that of graft-versus-host disease suggests that activa ted microchimeric cells may be a necessary factor in the pathogenesis of au toimmune diseases such as SSc.