title: Chronic rejection in lung allografts: immunohistological analysis of fibrogenesis.
abstract: In ongoing chronic rejection after lung transplantation, alveolar interstitial fibrosis develops. However, little is known about the mechanisms involved. In order to investigate these mechanisms, expression of extracellular matrix molecules (ECM) (undulin, decorin, tenascin, laminin, and fibronectin) and cytokines [transforming growth factor (TGF)-beta 1, TGF-beta 3, platelet-derived growth factor (PDGF), and PDGF receptor] were semiquantitatively evaluated in chronically rejected lung allografts, using standard immunohistochemical techniques. Additionally, the presence of macrophages was analysed. The present study demonstrates an increased infiltration of macrophages with a concomitant upregulation of cytokines (TGF-beta 1, TGF-beta 3, and PDGF) and an increased deposition of ECM in chronic lung rejection. These cytokines have an important role in the stimulation of fibroblasts which are a major source of ECM. Upregulated expression of ECM in the alveolar interstitial space leads to alveolar malfunction by thickening of the wall and, thus, is one of the causative factors of respiratory dysfunction in chronic lung graft rejection.
authors.affiliation: Klinik für Abdominal- und Transplantationschirurgie, Medizinische Hochschule Hannover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Hirabayashi
authors.forename: S
authors.initials: S
authors.lastname: Demertzis
authors.forename: J
authors.initials: J
authors.lastname: Schäfers
authors.forename: K
authors.initials: K
authors.lastname: Hoshino
authors.forename: B
authors.initials: B
authors.lastname: Nashan
mesh_terms: D000328:Adult; D002908:Chronic Disease; D016207:Cytokines / Q000032:analysis; D016326:Extracellular Matrix Proteins / Q000032:analysis; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007150:Immunohistochemistry; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D011658:Pulmonary Fibrosis / Q000209:etiology*; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D016326:Extracellular Matrix Proteins; D010982:Platelet-Derived Growth Factor