The role of innate immunity in the long-term outcome of lung transplantation

Kawashima, M; Juvet, S.

doi:10.21037/atm.2020.03.20

Cited by 26 publications

(20 citation statements)

References 145 publications

(181 reference statements)

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“…The latter could be attributed to the finding that in some centers the incidence of bronchiolitis obliterans syndrome (BOS)—one phenotype of chronic lung allograft dysfunction (CLAD)—was increased in patients who developed PGD grade 3 after LTx [ 24 , 25 , 26 , 27 ]. This association could be explained by the strong PGD-related inflammatory cascade that triggers allorecognition and possibly rejection of the lung grafts [ 28 , 29 , 30 , 31 ]. The effects of profibrotic mediators like Transforming Growth Factor β have also been suggested to explain the link between PGD and BOS [ 32 ].…”

Section: Pgd At Clinical Levelmentioning

confidence: 99%

“…The innate-adaptive interface possibly links the severity of PGD to the later development of CLAD [ 29 , 30 ]. The clinical phenotype with increasing and late PGD grade 3 reflects the activation of the innate and adaptive immunity that progressively injures the endothelial-epithelial alveolar membrane in the days following LTx.…”

Section: Pgd At Cellular Levelmentioning

confidence: 99%

See 1 more Smart Citation

A Focused Review on Primary Graft Dysfunction after Clinical Lung Transplantation: A Multilevel Syndrome

Slambrouck

Raemdonck

Vos

et al. 2022

Cells

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Primary graft dysfunction (PGD) is the clinical syndrome of acute lung injury after lung transplantation (LTx). However, PGD is an umbrella term that encompasses the ongoing pathophysiological and -biological mechanisms occurring in the lung grafts. Therefore, we aim to provide a focused review on the clinical, physiological, radiological, histological and cellular level of PGD. PGD is graded based on hypoxemia and chest X-ray (CXR) infiltrates. High-grade PGD is associated with inferior outcome after LTx. Lung edema is the main characteristic of PGD and alters pulmonary compliance, gas exchange and circulation. A conventional CXR provides a rough estimate of lung edema, while a chest computed tomography (CT) results in a more in-depth analysis. Macroscopically, interstitial and alveolar edema can be distinguished below the visceral lung surface. On the histological level, PGD correlates to a pattern of diffuse alveolar damage (DAD). At the cellular level, ischemia-reperfusion injury (IRI) is the main trigger for the disruption of the endothelial-epithelial alveolar barrier and inflammatory cascade. The multilevel approach integrating all PGD-related aspects results in a better understanding of acute lung failure after LTx, providing novel insights for future therapies.

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Section: Pgd At Clinical Levelmentioning

confidence: 99%

Section: Pgd At Cellular Levelmentioning

confidence: 99%

A Focused Review on Primary Graft Dysfunction after Clinical Lung Transplantation: A Multilevel Syndrome

Slambrouck

Raemdonck

Vos

et al. 2022

Cells

View full text Add to dashboard Cite

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“…Ultimately this leads to remodeling and fibrosis termed obliterative bronchiolitis, while other anatomical compartments of the lung remain relatively intact. Small airways review article by Kawashima and Juvet explains the details of innate immunity leading to CLAD (56). Similarly, gastroesophageal reflux (57,58) and air pollution (59,60) can induce local airway-centered inflammatory processes, leading to obliterative airway fibrosis.…”

Section: Mechanisms Of Bos (Ii): External Alloantigenindependent Stimuli Targeting Airwaysmentioning

confidence: 99%

“…Additionally, ischemic injury may direct the airway toward further immune-mediated injury and fibrosis as discussed above. The release of DAMPs from damaged or dying cells activate innate immunity (56); the release of cryptic autoantigens might promote the autoimmune-mediated mechanisms as discussed above (62).…”

Section: Mechanisms Of Bos (Iv): Ischemia and Early Post-transplant Eventsmentioning

confidence: 99%

Bronchiolitis obliterans syndrome and restrictive allograft syndrome after lung transplantation: why are there two distinct forms of chronic lung allograft dysfunction?

Sato¹

2020

Ann Transl Med

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Bronchiolitis obliterans syndrome (BOS) had been considered to be the representative form of chronic rejection or chronic lung allograft dysfunction (CLAD) after lung transplantation. In BOS, small airways are affected by chronic inflammation and obliterative fibrosis, whereas peripheral lung tissue remains relatively intact. However, recognition of another form of CLAD involving multiple tissue compartments in the lung, termed restrictive allograft syndrome (RAS), raised a fundamental question: why there are two phenotypes of CLAD? Increasing clinical and experimental data suggest that RAS may be a prototype of chronic rejection after lung transplantation involving both cellular and antibody-mediated alloimmune responses. Some cases of RAS are also induced by fulminant general inflammation in lung allografts.However, BOS involves alloimmune responses and the airway-centered disease process can be explained by multiple mechanisms such as external alloimmune-independent stimuli (such as infection, aspiration and air pollution), exposure of airway-specific autoantigens and airway ischemia. Localization of immune responses in different anatomical compartments in different phenotypes of CLAD might be associated with lymphoid neogenesis or the de novo formation of lymphoid tissue in lung allografts. Better understanding of distinct mechanisms of BOS and RAS will facilitate the development of effective preventive and therapeutic strategies of CLAD.

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“…IRI is driven by several inflammatory pathways (including release of reactive oxygen species, neutrophil activation, and production of proinflammatory factors) that are activated at the time of graft preservation and last until implantation. The activation of such pathways results in a significant damage of the alveolar capillary structures, which can lead to the development of early postoperative graft disfunction (PGD) and, ultimately, chronic lung allograft dysfunction (CLAD) [ 4 , 5 ]. In addition, hypothermic organ storage is also associated with oxidative stress and cell death in alveolar tissue, thus triggering the activation of proinflammatory pathways after lung transplantation [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Conditioned Medium from Human Amnion-Derived Mesenchymal Stromal/Stem Cells Attenuating the Effects of Cold Ischemia-Reperfusion Injury in an In Vitro Model Using Human Alveolar Epithelial Cells

Miceli

Bertani

Chinnici

et al. 2021

IJMS

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The clinical results of lung transplantation (LTx) are still less favorable than other solid organ transplants in both the early and long term. The fragility of the lungs limits the procurement rate and can favor the occurrence of ischemia-reperfusion injury (IRI). Ex vivo lung perfusion (EVLP) with Steen SolutionTM (SS) aims to address problems, and the implementation of EVLP to alleviate the activation of IRI-mediated processes has been achieved using mesenchymal stromal/stem cell (MSC)-based treatments. In this study, we investigated the paracrine effects of human amnion-derived MSCs (hAMSCs) in an in vitro model of lung IRI that includes cold ischemia and normothermic EVLP. We found that SS enriched by a hAMSC-conditioned medium (hAMSC-CM) preserved the viability and delayed the apoptosis of alveolar epithelial cells (A549) through the downregulation of inflammatory factors and the upregulation of antiapoptotic factors. These effects were more evident using the CM of 3D hAMSC cultures, which contained an increased amount of immunosuppressive and growth factors compared to both 2D cultures and encapsulated-hAMSCs. To conclude, we demonstrated an in vitro model of lung IRI and provided evidence that a hAMSC-CM attenuated IRI effects by improving the efficacy of EVLP, leading to strategies for a potential implementation of this technique.

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The role of innate immunity in the long-term outcome of lung transplantation

Cited by 26 publications

References 145 publications

A Focused Review on Primary Graft Dysfunction after Clinical Lung Transplantation: A Multilevel Syndrome

A Focused Review on Primary Graft Dysfunction after Clinical Lung Transplantation: A Multilevel Syndrome

Bronchiolitis obliterans syndrome and restrictive allograft syndrome after lung transplantation: why are there two distinct forms of chronic lung allograft dysfunction?

Conditioned Medium from Human Amnion-Derived Mesenchymal Stromal/Stem Cells Attenuating the Effects of Cold Ischemia-Reperfusion Injury in an In Vitro Model Using Human Alveolar Epithelial Cells

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