Ingraft chimerism in lung transplantation--a study in a porcine model of obliterative bronchiolitis.

Background: Bronchial epithelium is a target of the alloimmune response in lung transplantation, and intact epithelium may protect allografts from rejection and obliterative bronchiolitis (OB). Herein we study the influence of chimerism on bronchial epithelium and OB development in pigs.

Methods: A total of 54 immunosuppressed and unimmunosuppressed bronchial allografts were serially obtained 2-90 days after transplantation.

Local C-reactive protein expression in obliterative lesions and the bronchial wall in posttransplant obliterative bronchiolitis.

The local immunoreactivity of C-reactive protein (CRP) was studied in a heterotopic porcine model of posttranplant obliterative bronchiolitis (OB). Bronchial allografts and control autografts were examined serially 2-28 days after subcutaneous transplantation. The autografts stayed patent.

Epithelial tenascin predicts obliterative airway disease.

Background: Epithelial cell injury, inflammation, fibrosis and airway obliteration result in remodeling of terminal bronchi in post-transplant obliterative bronchiolitis. Tenascin as an extracellular matrix glycoprotein is expressed in several remodeling processes.

Methods: Heterotopic bronchial allografts of pigs were studied to assess tenascin expression during development of post-transplant obliterative bronchiolitis.

Platelet-derived growth factor, transforming growth factor-beta, and connective tissue growth factor in a porcine bronchial model of obliterative bronchiolitis.

The expression of platelet-derived growth factor (PDGF), transforming growth factor (TGF)-beta, and connective tissue growth factor (CTGF) and the effect of imatinib, an agent inhibiting PDGF receptors, were assessed in a porcine bronchial transplantation model of obliterative bronchiolitis (OB). Up-regulation of PDGF-A, PDGF receptors alpha and beta, and TGF-beta expression occurred in allografts, whereas PDGF-B and CTGF expression was similar in allo- and autografts. Imatinib modified the inflammatory responses and expression patterns of PDGF-A and PDGF receptors.

Immune cells in a heterotopic lamb-to-pig bronchial xenograft model.

We developed our porcine model to elucidate the cellular rejection mechanisms of xenografts. Bronchial segments from a donor lamb were implanted into domestic pigs. The immunosuppressive regimens consisted of no immusuppression, or of daily oral cyclosporine A (CsA) 15 mg/kg, or of everolimus, 1.

Matrix metalloproteinase induction in post-transplant obliterative bronchiolitis.

Background: Epithelial cell injury, inflammation, fibrosis, and airway obliteration are associated in post-transplant obliterative bronchiolitis. Fibrosis is a consequence of fibroblastic activity and of collagen deposition after disturbances in the balance of protein formation and degradation. Proteolytic enzymes such as the matrix metalloproteinases mediate degradation.

Cyclooxygenase-2 expression in experimental post-transplant obliterative bronchiolitis.

Epithelial cell injury, inflammation, progressive fibrosis, and airway obliteration are histological features of post-transplant obliterative bronchiolitis (OB). Cyclooxygenase (COX)-2 is expressed in acute and chronic inflammatory responses. Our aim was to elucidate the possible role of COX-2 in post-transplant OB by using a heterotopic bronchial porcine model.

Epithelial apoptosis in experimental obliterative airway disease after lung transplantation.

Background: Epithelial damage is an important feature in the pathogenesis of obliterative airway disease. We investigated the extent of epithelial apoptosis in this process in pig bronchial allografts.

Methods: The bronchial grafts (total, n = 200) were placed subcutaneously into recipients.

Tumor necrosis factor-alpha in a porcine bronchial model of obliterative bronchiolitis.

Background: In posttransplant obliterative bronchiolitis (OB), the major pathologic features are inflammation, epithelial cell injury, fibrosis, and obliteration of the small airways. Tumor necrosis factor (TNF)-alpha is a cytokine known to mediate and augment the inflammatory reaction and to enhance fibroblast proliferation. We assessed the role of TNF-alpha in the development of OB in our heterotopic porcine bronchial transplantation model.