Published ahead of print on March 9, 2006, doi:10.1164/rccm.200509-1381OC
© 2006 American Thoracic Society doi: 10.1164/rccm.200509-1381OC
Fibroblasts of Recipient Origin Contribute to Bronchiolitis Obliterans in Human Lung TransplantsInstitute of Pathology; Departments of Pneumology, and Hematology, Hemostaseology, and Oncology; Division of Thoracic and Cardiovascular Surgery, Medizinische Hochschule Hannover, Hannover, Germany; and Institute of Cell and Molecular Science, Diabetes and Metabolic Medicine, Queen Mary University of London, London, United Kingdom Correspondence and requests for reprints should be addressed to Ulrich Lehmann, Ph.D., Institute of Pathology, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. E-mail: lehmann.ulrich{at}mh-hannover.de 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 short tandem repeat–polymerase chain reaction–based genotyping. Combined immunofluorescence and fluorescence in situ hybridization for sex chromosomes was performed for independent confirmation in cases with appropriate sex mismatch (n = 2). Measurements and Main Results: The bronchiolitis obliterans lesions of all 12 lung transplant patients contained considerable numbers of recipient-derived fibroblasts (mean, 32%). The fibrosing pulmonary lesions of the two bone marrow–transplanted patients also displayed 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 in other organs.
Key Words: bone marrow–derived progenitors • in situ microchimerism • lung fibrosis • transplantation This article has been cited by other articles:
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