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Citations to this article

Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis
Ashok N. Babu, … , Norbert F. Voelkel, Mark R. Nicolls
Ashok N. Babu, … , Norbert F. Voelkel, Mark R. Nicolls
Published December 3, 2007
Citation Information: J Clin Invest. 2007;117(12):3774-3785. https://doi.org/10.1172/JCI32311.
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Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis

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Abstract

Small airway fibrosis (bronchiolitis obliterans syndrome) is the primary obstacle to long-term survival following lung transplantation. Here, we show the importance of functional microvasculature in the prevention of epithelial loss and fibrosis due to rejection and for the first time, relate allograft microvascular injury and loss of tissue perfusion to immunotherapy-resistant rejection. To explore the role of alloimmune rejection and airway ischemia in the development of fibroproliferation, we used a murine orthotopic tracheal transplant model. We determined that transplants were reperfused by connection of recipient vessels to donor vessels at the surgical anastomosis site. Microcirculation through the newly formed vascular anastomoses appeared partially dependent on VEGFR2 and CXCR2 pathways. In the absence of immunosuppression, the microvasculature in rejecting allografts exhibited vascular complement deposition, diminished endothelial CD31 expression, and absent perfusion prior to the onset of fibroproliferation. Rejecting grafts with extensive endothelial cell injury were refractory to immunotherapy. After early microvascular loss, neovascularization was eventually observed in the membranous trachea, indicating a reestablishment of graft perfusion in established fibrosis. One implication of this study is that bronchial artery revascularization at the time of lung transplantation may decrease the risk of subsequent airway fibrosis.

Authors

Ashok N. Babu, Tomohiro Murakawa, Joshua M. Thurman, Edmund J. Miller, Peter M. Henson, Martin R. Zamora, Norbert F. Voelkel, Mark R. Nicolls

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2007 Total
Citations: 3 3 4 2 3 4 5 5 1 9 7 3 7 4 3 3 1 1 68
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Citations to this article (68)

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bioRxiv 2024
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