Fibroblasts of Recipient Origin Contribute to Bronchiolitis Obliterans in Human Lung Transplants
| Autor: | Matthias Eder, Mairi Brittan, Hans Kreipe, Axel Haverich, Michael Mengel, Florian Länger, Tariq G. Fellous, Malcolm R. Alison, Ulrich Lehmann, Verena Bröcker, S. Milde, Tobias Welte, Martin Bredt |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Graft Rejection Male Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Pulmonary Fibrosis Bronchiolitis obliterans Critical Care and Intensive Care Medicine Intensive care medicine Humans Transplantation Homologous Child Bronchiolitis Obliterans In Situ Hybridization Fluorescence Microdissection Bone Marrow Transplantation Transplantation Chimera Lung medicine.diagnostic_test business.industry Microchimerism Fibroblasts medicine.disease Immunohistochemistry Tissue Donors Transplantation medicine.anatomical_structure Bronchiolitis Immunology Female business Lung Transplantation Fluorescence in situ hybridization |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine. 173:1276-1282 |
| ISSN: | 1535-4970 1073-449X |
| DOI: | 10.1164/rccm.200509-1381oc |
| Popis: | 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 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).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%).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. |
| Databáze: | OpenAIRE |
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