title: [Fibroblasts of recipient origin contribute to broncholitis obliterans in human lung transplants].
abstract: BACKGROUND
  The participation of circulating precursor cells in the development of experimental pulmonary fibrosing lesions in mice has been recently demonstrated.
  
  
  OBJECTIVE
  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).
  
  
  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.
authors.affiliation: Institut für Pathologie, Medizinische Hochschule, Hannover.
authors.forename: Verena
authors.initials: V
authors.lastname: Bröcker
authors.forename: Ulrich
authors.initials: U
authors.lastname: Lehmann
authors.forename: Florian
authors.initials: F
authors.lastname: Länger
authors.forename: Tariq G
authors.initials: TG
authors.lastname: Fellous
authors.forename: Michael
authors.initials: M
authors.lastname: Mengel
authors.forename: Mairi
authors.initials: M
authors.lastname: Brittan
authors.forename: Martin
authors.initials: M
authors.lastname: Bredt
authors.forename: Simone
authors.initials: S
authors.lastname: Milde
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.forename: Matthias
authors.initials: M
authors.lastname: Eder
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Alison
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
mesh_terms: D001706:Biopsy; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000473:pathology*; D005260:Female; D005347:Fibroblasts / Q000637:transplantation*; D005500:Follow-Up Studies; D006801:Humans; D016040:Lung Transplantation / Q000473:pathology*; D008297:Male; D018183:Transplantation Chimera