ArticleThe Annals of thoracic surgery2013
Rapamycin blocks fibrocyte migration and attenuates bronchiolitis obliterans in a murine model.
Article in The Annals of thoracic surgery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06018766 (A Randomized, Placebo-controlled Phase 2 Study to Demonstrate the Safety and Efficacy of the Addition of LAM-001 to Standard Immunosuppression Therapy for Chronic Lung Allograft Dysfunction), which is not on this map. Cited by 10 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Placebo-controlled Phase 2 Study to Demonstrate the Safety and Efficacy of the Addition of LAM-001 to Standard Immunosuppression Therapy for Chronic Lung Allograft Dysfunction (BOS).
Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Sirolimus suppresses circulating fibrocytes in idiopathic pulmonary fibrosis in a randomized controlled crossover trial.JCI insight · 2023Trial
- Article
- Article
- SOCS3 overexpression in T cells ameliorates chronic airway obstruction in a murine heterotopic tracheal transplantation model.Surgery today · 2019Article
- The emerging role of fibrocytes in ocular disorders.Stem cell research & therapy · 2018Review
- Rapamycin prevents bronchiolitis obliterans through increasing infiltration of regulatory B cells in a murine tracheal transplantation model.The Journal of thoracic and cardiovascular surgery · 2016Article
- Article
- Local origin of mesenchymal cells in a murine orthotopic lung transplantation model of bronchiolitis obliterans.The American journal of pathology · 2015Article
- Rapamycin promotes Schwann cell migration and nerve growth factor secretion.Neural regeneration research · 2014Article
- Short-course rapamycin treatment preserves airway epithelium and protects against bronchiolitis obliterans.The Annals of thoracic surgery · 2013Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundFibrocytes are integral in the development of fibroproliferative disease. The CXCL12/CXCR4 chemokine axis has been shown to play a central role in fibrocyte migration and the development of bronchiolitis obliterans (BO) after lung transplantation. Inhibition of the mammalian target of rapamycin (mTOR) pathway with rapamycin has been shown to decrease expression of both CXCR4 and its receptor agonist CXCL12. Thus, we hypothesized that rapamycin treatment would decrease fibrocyte trafficking into tracheal allografts and prevent BO.
methodsA total alloantigenic mismatch murine heterotopic tracheal transplant (HTT) model of BO was used. Animals were either treated with rapamycin or dimethyl sulfoxide (DMSO) for 14 days after tracheal transplantation. Fibrocyte levels were assessed by flow cytometry, and allograft neutrophil, CD3(+) T-cell, macrophage, and smooth muscle actin (SMA) levels were assessed by immunohistochemistry. Tracheal luminal obliteration was assessed on hematoxylin and eosin (H&E) stains.
resultsCompared with DMSO-treated controls, rapamycin-treated mice showed a significant decrease in fibrocyte levels in tracheal allografts. Fibrocyte levels in recipient blood showed a similar pattern, although it was not statistically significant. Furthermore, animals treated with rapamycin showed a significant decrease in tracheal allograft luminal obliteration compared with controls. Based on immunohistochemical analyses, populations of α-SMA-positive (α-SMA(+)) cells, neutrophils, CD3(+) T cells, and macrophages were all decreased in rapamycin-treated allografts versus DMSO controls.
conclusionsRapamycin effectively reduces recruitment of fibrocytes into tracheal allografts and mitigates development of tracheal luminal fibrosis. Further studies are needed to determine the cellular and molecular mechanisms that mediate the protective effect of rapamycin against BO.
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