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

Rationale: The participation of circulating precursor cells in the development of experimental pulmonary fibrosing lesions in mice has been recently demonstrated.

Objectives: This study analyzes whether circulating, bone marrow-derived fibroblastic precursor cells contribute to the development of fibrosing lesions in human lungs, especially bronchiolitis obliterans.

Methods: 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).

Measurements and main results: 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%).

Conclusions: 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.