Fibroblasts of recipient origin contribute to broncholitis obliterans in human lung transplants

Abstract The participation of circulating precursor cells in the development of experimental pulmonary fibrosing lesions in mice has been recently demonstrated. This study analyzes whether circulating, bone marrow-derived fibroblastic precursor cells contribute to the development of fibrosing lesions in human lungs, especially bronchiolitis obliterans. The occurrence of in situ-microchimerism in bronchiolitis obliterans lesions of human lung allografts (n = 12) as well as of autologous lung tissue from patients post bone marrow-transplantation (n = 2) was analyzed using laser-assisted microdissection after immunohistochemical labeling of leukocytes followed by STR-PCR-based genotyping. Combined immunofluorescence and fluorescence in situ hybridization for sex chromsomes was performed for independent confirmation in cases with appropriate sex mismatch (n = 2). The bronchiolitis obliterans lesions of all twelve lung transplant patients contained considerable numbers of recipient-derived fibroblasts (mean: 32 %). The fibrosing pulmonary lesions of the two bone marrow-transplanted patients displayed also clear in situ-microchimerism. The in situ detection methodology confirmed these results, although to a lower degree (6-16%). These data clearly demonstrate the involvement of circulating fibroblastic precursor cells in the development of human fibrosing lung lesions and provide evidence that these cells are most probably bone marrow-derived. These results may open new venues regarding the prevention of fibrosis in lung transplants and potentially other organs.