Fibroblasts of recipient origin contribute to bronchiolitis obliterans in human lung transplants.
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 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).


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.
Bröcker
Verena
V
Institute of Pathology, Department of Pneumology, Medizinische Hochschule Hannover, Hannover, Germany.
Länger
Florian
F
Fellous
Tariq G
TG
Mengel
Michael
M
Brittan
Mairi
M
Bredt
Martin
M
Milde
Simone
S
Welte
Tobias
T
Eder
Matthias
M
Haverich
Axel
A
Alison
Malcolm R
MR
Kreipe
Hans
H
Lehmann
Ulrich
U
D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D002648:Child; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D006084:Graft Rejection / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016040:Lung Transplantation / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D011658:Pulmonary Fibrosis / Q000473:pathology*; D014019:Tissue Donors; D018183:Transplantation Chimera / Q000235:genetics*; D014184:Transplantation, Homologous