Prevention of small airway obliteration in a swine heterotopic lung allograft model

Salminen, Ulla‐Stina; Maasilta, Paula; Taskinen, Eero; Alho, H; Ikonen, Tuija; Harjula, Ari

doi:10.1016/s1053-2498(99)00118-7

Cited by 34 publications

(15 citation statements)

References 25 publications

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“…In our porcine model, OB developed invariably in allografts, while autografts stayed patent, as expected [19, 26]. The histological changes were similar to those seen in human OB [2, 27] and in rodent models [28, 29].…”

Section: Discussionsupporting

confidence: 81%

Local C-Reactive Protein Expression in Obliterative Lesions and the Bronchial Wall in Posttransplant Obliterative Bronchiolitis

Päiväniemi

Maasilta

Vainikka

et al. 2009

Mediators of Inflammation

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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. In the allografts, proliferation of inflammatory cells (P < .0001) and fibroblasts (P = .02) resulted in occlusion of the bronchial lumens (P < .01). Influx of CD4+ (P < .001) and CD8+ (P < .0001) cells demonstrated allograft immune response. CRP positivity simultaneously increased in the bronchial walls (P < .01), in macrophages, myofibroblasts, and endothelial cells. Local CRP was predictive of features characteristic of OB (R = 0.456–0.879, P < .05−P < .0001). Early obliterative lesions also showed CRP positivity, but not mature, collagen-rich obliterative plugs (P < .05). During OB development, CRP is localized in inflammatory cells, myofibroblasts and endothelial cells probably as a part of the local inflammatory response.

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Section: Discussionsupporting

confidence: 81%

Local C-Reactive Protein Expression in Obliterative Lesions and the Bronchial Wall in Posttransplant Obliterative Bronchiolitis

Päiväniemi

Maasilta

Vainikka

et al. 2009

Mediators of Inflammation

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“…For example, one recent paper emphasized the increase in vascularity of segmental bronchi as a factor contributing to luminal attenuation in BOS (46). Furthermore many xenograft paper have described morphologic changes similar to those observed in our patients, namely those characterized by progressive epithelial and cartilage destruction with secondary fibroplasias involving the segmental bronchi (47,48).…”

Section: Discussionsupporting

confidence: 77%

Association of Humoral Immunity and Bronchiolitis Obliterans Syndrome

Magro¹,

Ross²,

Kelsey³

et al. 2003

American Journal of Transplantation

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Animal studies have shown that blockade of complement may reduce the severity of and/or prevent the development of bronchiolitis obliterans syndrome (BOS), suggesting a role for complement activation. We explored the hypothesis that humoral immunity plays a role in the evolution of BOS. Thirteen unilateral lung transplant patients with BOS defined the patient population. Fresh frozen tissue was analyzed for deposition of C1q, C4d, C5b‐9 and immunoglobulin (IgG, IgM, IgA). An indirect immunofluorescent assay was also conducted with patient serum against cytospins of the pulmonary endothelium. In each case the biopsies showed a microvascular injury syndrome involving the bronchial wall characterized by one or more of hemorrhage, fibrin deposition, and endothelial cell necrosis. Other features included bronchial epithelial and chondrocyte necrosis. The end‐stage lesion was a thinned bronchial epithelial lining mural fibrosis. Immunofluorescent analysis showed deposition of C1q, C3, C4d, C5b‐9, and immunoglobulin in the bronchial epithelium, chondrocytes, basement membrane zone of the bronchial epithelium, and bronchial wall microvasculature. The indirect antiendothelial cell antibody assay was positive in all tested. Humoral immunity may play a role in the pathogenesis of BOS; the antigenic targets include the bronchial wall microvasculature, bronchial epithelium, and chondrocytes.

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“…Preliminary data in animals specifically support the evaluation of these agents in lung transplant recipients, since everolimus prevents acute allograft rejection in rat models [121] and prevents epithelial destruction and luminal obliteration in a porcine heterotopic bronchial allograft model [122].…”

Section: Sirolimus and Everolimusmentioning

confidence: 95%

Immunosuppressive therapy after human lung transplantation

Knoop¹,

Haverich²,

Fischer³

2003

Eur Respir J

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numbers of lung transplantation (LTx) were performed with or without induction therapy with antilymphocyte antibodies, monoclonal anti-CD3 antibody or anti-interleukin-2-receptor monoclonal antibodies. It remains to be established if induction therapy after LTx is beneficial or deleterious for long-term graft and patient survival.The vast majority of lung transplant recipients receive a triple-drug maintenance regimen including a calcineurin inhibitor, a cell-cycle inhibitor and steroids. Equal proportions receive cyclosporin A (CsA) and tacrolimus (Tac). There is also a trend to prescribe mycophenolate mofetil (MMF) instead of azathioprine (Aza). Steroid withdrawal is uncommon even 5 yrs after transplantation.The superiority of Tac over CsA as a maintenance agent has not been established to date, and the administration of MMF instead of Aza in combination with CsA and steroids did not improve graft or patient survival in a recent international, prospective, randomised, controlled trial.Shift from cyclosporin A to tacrolimus has emerged as the first treatment step of refractory acute rejection followed by high-dose steroids or antilymphocyte agents, total lymphoid irradiation or photopheresis. The treatment of chronic rejection remains deceptive and includes varied strategies such as modification of the maintenance regimen, addition of inhaled immunosuppressants and/or total lymphoid irradiation and photopheresis. Eur Respir J 2004; 23: 159-171.

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Prevention of small airway obliteration in a swine heterotopic lung allograft model

Cited by 34 publications

References 25 publications

Local C-Reactive Protein Expression in Obliterative Lesions and the Bronchial Wall in Posttransplant Obliterative Bronchiolitis

Local C-Reactive Protein Expression in Obliterative Lesions and the Bronchial Wall in Posttransplant Obliterative Bronchiolitis

Association of Humoral Immunity and Bronchiolitis Obliterans Syndrome

Immunosuppressive therapy after human lung transplantation

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