ArticleXenotransplantation2018
P- and E-selectin receptor antagonism prevents human leukocyte adhesion to activated porcine endothelial monolayers and attenuates porcine endothelial damage.
Article in Xenotransplantation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Pig Lung Xenotransplantation: Barriers on the Road to Clinical Translation.Transplant international : official journal of the European Society for Organ Transplantation · 2025Review
- Inflammation Control and Tumor Growth Inhibition of Ovarian Cancer by Targeting Adhesion Molecules of E-Selectin.Cancers · 2023Article
- Knock-out of N-glycolylneuraminic acid attenuates antibody-mediated rejection in xenogenically perfused porcine lungs.Xenotransplantation · 2022Article
- Pig heart and lung xenotransplantation: Present status.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2022Article
- Effects of human TFPI and CD47 expression and selectin and integrin inhibition during GalTKO.hCD46 pig lung perfusion with human blood.Xenotransplantation · 2022Article
- Pig-to-baboon lung xenotransplantation: Extended survival with targeted genetic modifications and pharmacologic treatments.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Article
- Humanized von Willebrand factor reduces platelet sequestration in ex vivo and in vivo xenotransplant models.Xenotransplantation · 2021Article
- Directional homing of glycosylation-modified bone marrow mesenchymal stem cells for bone defect repair.Journal of nanobiotechnology · 2021Article
- Targeting E-selectin to Tackle Cancer Using Uproleselan.Cancers · 2021Review
- Minimizing Ischemia Reperfusion Injury in Xenotransplantation.Frontiers in immunology · 2021Review
- From Metabolic Syndrome to Neurological Diseases: Role of Autophagy.Frontiers in cell and developmental biology · 2021Review
- The vascular bone marrow niche influences outcome in chronic myeloid leukemiaHaematologica · 2020Article
- The Bone Marrow Niche - The Tumor Microenvironment That Ensures Leukemia Progression.Advances in experimental medicine and biology · 2020Review
- "Stuck on sugars - how carbohydrates regulate cell adhesion, recognition, and signaling".Glycoconjugate journal · 2019Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAlongside the need to develop more effective and less toxic immunosuppression, the shortage of human organs available for organ transplantation is one of the major hurdles facing the field. Research into xenotransplantation, as an alternative source of organs, has unveiled formidable challenges. Porcine lungs perfused with human blood rapidly sequester the majority of circulating neutrophils and platelets, which leads to inflammation and organ failure within hours, and is not significantly attenuated by genetic modifications to the pig targeted to diminish antibody binding and complement and coagulation cascade activation.
methodsHere, we model the interaction of freshly isolated human leukocytes with xenotransplanted vasculature under physiologic flow conditions using microfluidic channels coated with porcine endothelial cells. Both isolated human neutrophils and whole human blood were perfused over transgenic pig aortic endothelial cells that had been activated with rhTNF-α or rhIL-4 using the BioFlux system. Novel compounds GMI-1271 and rPSGL1.Fc were tested as E- and P- selectin antagonists, respectively. Cellular adhesion and rolling events were tracked using FIJI (imageJ).
resultsPorcine endothelium activated with either rhTNF-α or rhIL-4 expressed high amounts of selectins, to which isolated human neutrophils readily rolled and tethered. Both E-and P-selectin antagonism significantly reduced the number of neutrophils rolling and rolling distance in a dose-dependent manner, with near total inhibition at higher doses (P < .001). Similarly, with whole human blood, selectin blocking compounds exhibited dose-dependent inhibition of prevalent leukocyte adhesion and severe endothelial injury (Untreated: 394 ± 97 PMNs/hpf, 57 ± 6% loss EC; GMI1271+rPSGL1.Fc: 23 ± 9 PMNs/hpf, 8 ± 6% loss EC P < .01).
conclusionsSelectin blockade may be useful as part of an integrated strategy to prevent neutrophil-mediated organ xenograft injury, especially during the early time points following reperfusion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.