ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2015
Cyclosporine Does Not Prevent Microvascular Loss in Transplantation but Can Synergize With a Neutrophil Elastase Inhibitor, Elafin, to Maintain Graft Perfusion During Acute Rejection.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- cGAS/STING signalling in macrophages aggravates obliterative bronchiolitis via an IFN-α-dependent mechanism after orthotopic tracheal transplantation in mice.Clinical and translational medicine · 2025Article
- Targeting Interleukin-10 Restores Graft Microvascular Supply and Airway Epithelium in Rejecting Allografts.International journal of molecular sciences · 2022Article
- Effect of MMF Immunosuppression Based on CNI Reduction on CNI-Related Renal Damage after Lung Transplantation.Journal of healthcare engineering · 2022Article
- Article
- Differential effects of the immunosuppressive calcineurin inhibitors cyclosporine-A and tacrolimus on ovulation in a murine model.Human reproduction open · 2021Article
- Antioxidative properties ofToxicology reports · 2021Article
- iPSC-derived MSC therapy induces immune tolerance and supports long-term graft survival in mouse orthotopic tracheal transplants.Stem cell research & therapy · 2019Article
- Airway hypoxia in lung transplantation.Current opinion in physiology · 2019Article
- Article
- IL-17A deficiency mitigates bleomycin-induced complement activation during lung fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Potential Mechanisms Underlying TGF-β-mediated Complement Activation in Lung Fibrosis.Cellular & molecular medicine: open access · 2017Article
- Contribution of the anaphylatoxin receptors, C3aR and C5aR, to the pathogenesis of pulmonary fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Microvascular injury after lung transplantation.Current opinion in organ transplantation · 2016Review
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Authors and funding
12 authors.
Funding
Abstract
The loss of a functional microvascular bed in rejecting solid organ transplants is correlated with fibrotic remodeling and chronic rejection; in lung allografts, this pathology is predicted by bronchoalveolar fluid neutrophilia which suggests a role for polymorphonuclear cells in microcirculatory injury. In a mouse orthotopic tracheal transplant model, cyclosporine, which primarily inhibits T cells, failed as a monotherapy for preventing microvessel rejection and graft ischemia. To target neutrophil action that may be contributing to vascular injury, we examined the effect of a neutrophil elastase inhibitor, elafin, on the microvascular health of transplant tissue. We showed that elafin monotherapy prolonged microvascular perfusion and enhanced tissue oxygenation while diminishing the infiltration of neutrophils and macrophages and decreasing tissue deposition of complement C3 and the membrane attack complex, C5b-9. Elafin was also found to promote angiogenesis through activation of the extracellular signal-regulated kinase (ERK) signaling pathway but was insufficient as a single agent to completely prevent tissue ischemia during acute rejection episodes. However, when combined with cyclosporine, elafin effectively preserved airway microvascular perfusion and oxygenation. The therapeutic strategy of targeting neutrophil elastase activity alongside standard immunosuppression during acute rejection episodes may be an effective approach for preventing the development of irreversible fibrotic remodeling.
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