Obliterative airway remodelling in transplanted and non-transplanted lungs.
Obliterative airway remodelling is a morphological sequence in a variety of pulmonary diseases. Notably, bronchiolitis obliterans represents one of the key complications of lung transplantation, induced by (immigrating) myofibroblasts. A comparative expression analysis of obliterative airway remodelling in transplanted and non-transplanted patients has not been reported so far. Obliterated and unremodelled airways from explanted lungs (n = 19) from patients suffering from chronic allograft dysfunction, infection, graft-versus-host disease and toxic exposure were isolated by laser-assisted microdissection. Airways from lung allografts harvested shortly before and after transplantation (n = 4) as well as fibroblastic foci from lungs with interstitial pulmonary fibrosis (n = 4) served as references. Pre-amplified cDNA was analysed by quantitative real-time RT-PCR for expression of fibrosis, inflammation and apoptosis-associated genes. Composition of infiltrating cells and protein expression were assessed by conventional histology and immunohistochemistry. Bronchiolitis obliterans in transplanted patients showed a significant increase of BMP-7 expression (p = 0.0141 compared with controls), while TGF-beta1 and FGF-2 as well as BMP-4 and BMP-7 were up-regulated in fibroblastic foci in interstitial pulmonary fibrosis (p < 0.0424 compared with controls). Regarding other fibrosis-associated genes (BMP-6, SMAD-3, CASP-3 and CASP-9, FASLG, NF-KB1, IL-1 and IL-2) as well as cellularity and cellular composition, no significant differences between obliterative airway remodelling in transplanted and non-transplanted patients could be shown. Obliterative airway remodelling in lung allografts and in non-transplanted patients share many morphological and genetic traits. BMPs, especially BMP-7, warrant further investigation as possible markers for the aggravation of airway remodelling.
Jonigk
Danny
D
Institute of Pathology, Hannover Medical School, 30625 Hannover, Germany. jonigk.danny@mh-hannover.de
Theophile
Katharina
K
Hussein
Kais
K
Bock
Oliver
O
Lehmann
Ulrich
U
Bockmeyer
Clemens L
CL
Gottlieb
Jens
J
Fischer
Stefan
S
Simon
Andre
A
Welte
Tobias
T
Maegel
Lavinia
L
Kreipe
Hans
H
Laenger
Florian
F
D000293:Adolescent; D000328:Adult; D056151:Airway Remodeling / Q000502:physiology*; D015415:Biomarkers / Q000032:analysis; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism; D001989:Bronchiolitis Obliterans / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007834:Lasers; D016040:Lung Transplantation / Q000009:adverse effects* / Q000473:pathology*; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D015415:Biomarkers; D055419:Bone Morphogenetic Protein 7