Innate and adaptive immune responses in obliterative airway disease in rat tracheal allografts

Ropponen, Jussi O.; Syrjälä, S.; Krebs, R.; Nykänen, Antti; Tikkanen, Jussi; Lemström, Karl

doi:10.1016/j.healun.2010.12.011

Cited by 12 publications

(11 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This was also observed by others in a cardiac allograft model (43). Another study, using a rat HTT model in the omentum, concluded that CsA treatment inhibited both Th1 and Th17 pathways (44). This apparent discordance might be related to the model and methodology.…”

Section: Of Cd8mentioning

confidence: 52%

Cyclosporine A Drives a Th17- and Th2-Mediated Posttransplant Obliterative Airway Disease

Lemaître

Vokaer

Charbonnier

et al. 2013

American Journal of Transplantation

View full text Add to dashboard Cite

Calcineurin-inhibitor refractory bronchiolitis obliterans (BO) represents IntroductionIntroduction of calcineurin inhibitors (CNIs) has significantly reduced acute rejection rates and was anticipated to have implications for long-term prognosis (1). However, current data indicate that, contrary to expectations, long-term survival rates poorly reflect short-term improvements. Lung transplantation (LTx), which remains the only therapeutic approach for end-stage lung failure, is no exception. The 1-year survival rate for LTx is >80% whereas the 10-year survival rate does not exceed 23% (1). Bronchiolitis obliterans (BO) is the leading cause of late failure after lung transplantation. Although immune mechanisms including T cell-mediated alloreactivity and autoimmunity appear to be central to the pathology of BO, detailed mechanisms remain poorly understood. Recent reports in rodents and in humans suggest a role for the involvement of Th2 (2) and Th17 (3,4) in the pathogenesis of BO, although the latter may still be controversial (5). Whereas the large majority of lung transplant recipients receive CNI-based immunosuppressive regimens, more than 50% develop BO (6). This suggests that mechanisms underlying BO resist treatment by CNIs or could even be promoted by these drugs.

show abstract

Section: Of Cd8mentioning

confidence: 52%

Cyclosporine A Drives a Th17- and Th2-Mediated Posttransplant Obliterative Airway Disease

Lemaître

Vokaer

Charbonnier

et al. 2013

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…In this model, even the epithelium in syngrafts suffers extensive early damage and then recovers in the absence of alloimmune activation. 22 Earlier, the increased vascular endothelial growth factor-A expression was shown to improve epithelial recovery in this model. 24 Furthermore, allograft overexpression of HIF-1α promotes repair of airway microvasculature through the induced expression of pro-angiogenic factors in mice.…”

Section: Figurementioning

confidence: 76%

“…On the basis of our previous studies with the tracheal allograft model, 22 we chose to investigate the mRNA expression of allografts at 10 days, at the time of peak of alloimmune activation. The mRNA expression of Treg transcription factor forkhead box P3 (FoxP3) was significantly increased (p ¼ 0.002), meanwhile the mRNA expression of Th17-related cytokine interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, and heme oxygenase-1 (HO-1) was significantly reduced in mVHL -/-(p ¼ 0.005, p ¼ 0.005, and p ¼ 0.014; Figure 4A-C).…”

Section: Resultsmentioning

confidence: 99%

“…17,22 In syngrafts, ischemia induces a self-limiting, alloantigenindependent innate immune response, the epithelium recovers completely, and no OAD develops. 22 In the allografts without immunosuppression, the early ischemic injury is followed by a predominantly pro-inflammatory milieu. Alloantigen-dependent Th1 and Th17 responses peak at 7 to 10 days, followed by progressive epithelial damage and a nearly total airway occlusion 30 days after transplantation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Increased myeloid cell hypoxia-inducible factor-1 delays obliterative airway disease in the mouse

Ropponen

Keränen

Raissadati

et al. 2016

The Journal of Heart and Lung Transplantation

Self Cite

View full text Add to dashboard Cite

“…Subsequent studies in rats have shown that inhalation exposure to diacetyl, or to the chemically-related flavoring 2,3-pentanedione, causes airway lesions that are histopathologically similar to OB lesions in humans (Morgan et al, 2016, 2012). Although innate and adaptive immune responses, tissue ischemia associated with transplantation, and chronic epithelial injury are known to contribute to the development of OB lesions (Babu et al, 2007; Fernandez et al, 2004; O’Koren et al, 2013; Ropponen et al, 2011; Snell and Westall 2010), the etiology and pathogenesis of this disease are unclear.…”

Section: Introductionmentioning

confidence: 99%

Pathology of diacetyl and 2,3-pentanedione airway lesions in a rat model of obliterative bronchiolitis

Flake

Morgan

2017

Toxicology

View full text Add to dashboard Cite

Inhalation of diacetyl vapors by workers has been associated with obliterative bronchiolitis (OB), a poorly understood fibroproliferative disease of the small airways. Significant insights into the pathogenesis of OB have been obtained through the use of a rat model. Inhalation exposure of rats to diacetyl or 2,3-pentanedione, a related flavoring agent, can cause severe injury to the airway epithelium and underlying basement membrane. Repeated exposure to diacetyl or 2,3-pentanedione leads to aberrant repair, fibroproliferation and partial to complete occlusion of the airway lumen. Fibroproliferative lesions in rat airways were found to include both intraluminal polyps and circumferential intramural lesions. Intraluminal polyps have been observed to form secondary attachments spanning the airway lumen causing increasing obstruction. These airway lesions in rats are accompanied by inflammation in the form of peribronchial and perivascular infiltrates of lymphocytes, eosinophils and neutrophils. Diacety-linduced OB lesions in the rat are similar to OB lesions in humans and provide a good model for studying the pathogenesis of this disease.

show abstract

Innate and adaptive immune responses in obliterative airway disease in rat tracheal allografts

Cited by 12 publications

References 47 publications

Cyclosporine A Drives a Th17- and Th2-Mediated Posttransplant Obliterative Airway Disease

Cyclosporine A Drives a Th17- and Th2-Mediated Posttransplant Obliterative Airway Disease

Increased myeloid cell hypoxia-inducible factor-1 delays obliterative airway disease in the mouse

Pathology of diacetyl and 2,3-pentanedione airway lesions in a rat model of obliterative bronchiolitis

Contact Info

Product

Resources

About