Obliterative airway remodelling in transplanted and non-transplanted lungs

Virchows Arch. 2010 Sep;457(3):369-80. doi: 10.1007/s00428-010-0949-x. Epub 2010 Jul 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Airway Remodeling / physiology*
  • Biomarkers / analysis
  • Bone Morphogenetic Protein 7 / genetics
  • Bone Morphogenetic Protein 7 / metabolism
  • Bronchiolitis Obliterans / genetics*
  • Bronchiolitis Obliterans / pathology*
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Lasers
  • Lung Transplantation / adverse effects*
  • Lung Transplantation / pathology*
  • Male
  • Microdissection
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction
  • Young Adult

Substances

  • Biomarkers
  • Bone Morphogenetic Protein 7