Lymphatic Vessels: The Next Frontier in Lung Transplant

Cui, Ye; Liu, Kaifeng; Lamattina, Anthony M.; Visner, Gary; El–Chemaly, Souheil

doi:10.1513/annalsats.201606-465mg

Cited by 27 publications

(19 citation statements)

References 83 publications

(80 reference statements)

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“…Furthermore, during lung transplant surgery, the pulmonary lymphatic vessel continuum is completely disrupted, and, as a result, lymphatic drainage function is severely compromised. After transplantation, the regeneration of an effective lymphatic drainage system plays a crucial role in maintaining interstitial fluid balance in the lung allograft, which could also contribute to the observed difference in B‐lines at 3500 m .…”

Section: Discussionmentioning

confidence: 99%

High altitude trekking after lung transplantation: a prospective study using lung ultrasound to detect comets tails for interstitial pulmonary edema in lung transplant recipients and healthy volunteers

et al. 2018

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Clinical trial registration number: NCT03117686 (clinicaltrials.gov). SUMMARYThe intensity of physical activity which can be tolerated after lung transplantation and the tolerance to prolonged exercise at high altitude are poorly investigated. Lung ultrasound comet tails have been used in the diagnosis of interstitial pulmonary edema and high pulmonary altitude edema. The aim was to assess the number of lung ultrasound comet tails and to monitor changes in the optic nerve sheath diameter (ONSD) during a climb to the top of Mount Kilimanjaro in 10 lung transplant recipients and 10 healthy controls at three different altitude levels: 1360, 3505, 4900 m. Lung transplant recipients showed a constant increase in comet tail scores with altitude, whereas control subjects only showed an increase at the highest measurement point. Differences between groups (transplant versus control) reached significance only after the first ascend: 0.9 (95% CI: À0.41; 2.21) vs. 0.1 (95% CI: À0.12; 0.32) (P = 0.2; 1360 m), 2.33 (95% CI: 0.64; 4.02) vs. 0.3 (95% CI: À0.18; 0.78) (P = 0.04; 3505 m), and 4.11 (95% CI: 0.13; 0.34) vs. 2.9 (95% CI: 0.49; 5.31) (P = 0.15; 4900 m); ONSD increased significantly in both groups from 3.53 (95% CI: 0.34; 0.66) at 1360 m to 4.11 (95% CI: 0.36; 0.71) at 4900 m (P < 0.05). Lungs of transplant recipients are able to adapt to altitude and capable of performing prolonged exercise at high altitude after slow ascend.

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Section: Discussionmentioning

confidence: 99%

High altitude trekking after lung transplantation: a prospective study using lung ultrasound to detect comets tails for interstitial pulmonary edema in lung transplant recipients and healthy volunteers

et al. 2018

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“…The lymphatic system not only elicits anti-tumor immune responses but also promotes tolerance against tumors (Chen and Mellman, 2017). Recent studies provided evidence that LECs participate in the induction of peripheral tolerance through diverse mechanisms, under both physiological and pathological conditions (Card et al, 2014;Randolph et al, 2016;Cui et al, 2017). Because LECs express peripheral tissue antigens and major histocompatibility complex (MHC) molecules, they can directly recognize and suppress T cell activation when the expression levels of inhibitory receptor programmed death-ligand 1 (PD-L1) are high and those of co-stimulatory molecules are low (Lee et al, 2007;Nichols et al, 2007;Malhotra et al, 2012;Tewalt et al, 2012).…”

Section: Lymphatic Vessels In Tumor Immunobiologymentioning

confidence: 99%

Lymphatic vasculature in tumor metastasis and immunobiology

Jiang

2019

J. Zhejiang Univ. Sci. B

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Lymphatic vessels are essential for tissue fluid homeostasis, immune cell trafficking, and intestinal lipid absorption. The lymphatics have long been recognized to serve as conduits for distant tumor dissemination. However, recent findings suggest that the regional lymphatic vasculature also shapes the immune microenvironment of the tumor mass and potentiates immunotherapy. This review discusses the role of lymphatic vessels in tumor metastasis and tumor immunity.

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“…The lymphatic vasculature plays important roles in lung homeostasis, by clearing immune cells and draining interstitial fluid (Alitalo, 2011 ; Cui et al, 2017 ; Stump et al, 2017 ). The role of the lymphatic vasculature in acute and chronic lung rejection is only beginning to be unraveled.…”

Section: Introductionmentioning

confidence: 99%

FK506 induces lung lymphatic endothelial cell senescence and downregulates LYVE-1 expression, with associated decreased hyaluronan uptake

Shrestha

Cho

Stump

et al. 2020

Mol Med

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Background: Therapeutic lymphangiogenesis in an orthotopic lung transplant model has been shown to improve acute allograft rejection that is mediated at least in part through hyaluronan drainage. Lymphatic vessel endothelial hyaluronan receptor (LYVE-1) expressed on the surface of lymphatic endothelial cells plays important roles in hyaluronan uptake. The impact of current immunosuppressive therapies on lung lymphatic endothelial cells is largely unknown. We tested the hypothesis that FK506, the most commonly used immunosuppressant after lung transplantation, induces lung lymphatic endothelial cell dysfunction. Methods: Lung lymphatic endothelial cells were cultured in vitro and treated with FK506. Telomerase activity was measured using the TRAP assay. Protein expression of LYVE-1 and senescence markers p21 and β-galactosidase was assessed with western blotting. Matrigel tubulation assay were used to investigate the effects of FK506 on TNF-αinduced lymphangiogenesis. Dual luciferase reporter assay was used to confirm NFAT-dependent transcriptional regulation of LYVE-1. Flow cytometry was used to examine the effects of FK506 on LYVE-1 in precision-cut-lungslices ex vivo and on hyaluronan uptake in vitro. Results: In vitro, FK506 downregulated telomerase reverse transcriptase expression, resulting in decreased telomerase activity and subsequent induction of p21 expression and cell senescence. Treatment with FK506 decreased LYVE-1 mRNA and protein levels and resulted in decreased LEC HA uptake. Similar result showing reduction of LYVE-1 expression when treated with FK506 was observed ex vivo. We identified a putative NFAT binding site on the LYVE-1 promoter and cloned this region of the promoter in a luciferase-based reporter construct. We showed that this NFAT binding site regulates LYVE-1 transcription, and mutation of this binding site blunted FK506-dependent downregulation of LYVE-1 promoter-dependent transcription. Finally, FK506-treated lymphatic endothelial cells show a blunted response to TNF-α-mediated lymphangiogenesis.

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Lymphatic Vessels: The Next Frontier in Lung Transplant

Cited by 27 publications

References 83 publications

High altitude trekking after lung transplantation: a prospective study using lung ultrasound to detect comets tails for interstitial pulmonary edema in lung transplant recipients and healthy volunteers

High altitude trekking after lung transplantation: a prospective study using lung ultrasound to detect comets tails for interstitial pulmonary edema in lung transplant recipients and healthy volunteers

Lymphatic vasculature in tumor metastasis and immunobiology

FK506 induces lung lymphatic endothelial cell senescence and downregulates LYVE-1 expression, with associated decreased hyaluronan uptake

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