title: Obliterative airway remodelling in transplanted and non-transplanted lungs.
abstract: 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.
authors.affiliation: Institute of Pathology, Hannover Medical School, 30625 Hannover, Germany. jonigk.danny@mh-hannover.de
authors.forename: Danny
authors.initials: D
authors.lastname: Jonigk
authors.forename: Katharina
authors.initials: K
authors.lastname: Theophile
authors.forename: Kais
authors.initials: K
authors.lastname: Hussein
authors.forename: Oliver
authors.initials: O
authors.lastname: Bock
authors.forename: Ulrich
authors.initials: U
authors.lastname: Lehmann
authors.forename: Clemens L
authors.initials: CL
authors.lastname: Bockmeyer
authors.forename: Jens
authors.initials: J
authors.lastname: Gottlieb
authors.forename: Stefan
authors.initials: S
authors.lastname: Fischer
authors.forename: Andre
authors.initials: A
authors.lastname: Simon
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.forename: Lavinia
authors.initials: L
authors.lastname: Maegel
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
authors.forename: Florian
authors.initials: F
authors.lastname: Laenger
mesh_terms: 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
chemical_list: D015415:Biomarkers; D055419:Bone Morphogenetic Protein 7