Human CD31 on porcine cells suppress xenogeneic neutrophil‐mediated cytotoxicity via the inhibition of <scp>NET</scp>osis

Wang, Han-Tang; Maeda, Akira; Sakai, Rieko; Lo, Pei‐Chi; Takakura, Chihiro; Jiaravuthisan, Patmika; Shabri, Afifah Mod; Matsuura, Ryohei; Kodama, Tatsuhiko; Hiwatashi, Shohei; Eguchi, Hiroshi; Okuyama, Hiroomi; Miyagawa, Shuji

doi:10.1111/xen.12396

Cited by 18 publications

(11 citation statements)

References 60 publications

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“…8,9 Most recently, another deleterious immune activation process in xenotransplantation has gained prominence, namely the ejection of DNA-histone complexes into the extracellular space from activated neutrophils to form neutrophil extracellular traps (NETs). 10,11 Increased NET formation is well known in various clinical conditions, including sepsis, trauma, autoimmune diseases, deep vein thrombosis, atherosclerosis, and thrombotic microangiopathy. 12,13 Because multiple nosologies share humoral and cellular activation pathways, we asked whether TAVI increases circulating soluble suppression of tumorigenicity-2 (sST2) and its counterpart interleukin (IL)-33, a known biological alarmin that would serve as an additional biological marker for ongoing inflammatory processes.…”

Section: Central Messagementioning

confidence: 99%

Inflammatory immune response in recipients of transcatheter aortic valves

et al. 2021

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Objective: Transcatheter aortic valve implantation (TAVI) is rapidly replacing cardiac surgery due to its minimal invasiveness and practicality. Midterm immunological studies on the biocompatibility of galactose-alpha-1,3-galactose (a-Gal)carrying bioprosthetic heart valves for TAVI are not available. In this study we investigated whether bioprosthetic heart valves employed for TAVI augment an a-Gal-specific antibody-dependent and antibody-independent immune response 3 months after TAVI implantation. PERSPECTIVENext-generation transcatheter aortic valve implantation, deficient for Gal, will show whether immune activity can be dampened with the potential consequence of increased valve durability.See Commentaries on pages 97 and 99.

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Section: Central Messagementioning

confidence: 99%

Inflammatory immune response in recipients of transcatheter aortic valves

et al. 2021

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“…Wang et al. recently reported that the ectopic expression of human CD31 on porcine cells suppress xenogeneic neutrophil NETosis and cytotoxicity ( 89 ). CD31 (PECAM-1) is well known as an adhesion molecule and is ubiquitously expressed by various inflammatory cells ( 90 ).…”

Section: Inhibition Of Neutrophil-mediated Xenogeneic Rejectionmentioning

confidence: 99%

The Innate Cellular Immune Response in Xenotransplantation

et al. 2022

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Xenotransplantation is very attractive strategy for addressing the shortage of donors. While hyper acute rejection (HAR) caused by natural antibodies and complement has been well defined, this is not the case for innate cellular xenogeneic rejection. An increasing body of evidence suggests that innate cellular immune responses contribute to xenogeneic rejection. Various molecular incompatibilities between receptors and their ligands across different species typically have an impact on graft outcome. NK cells are activated by direct interaction as well as by antigen dependent cellular cytotoxicity (ADCC) mechanisms. Macrophages are activated through various mechanisms in xenogeneic conditions. Macrophages recognize CD47 as a “marker of self” through binding to SIRPα. A number of studies have shown that incompatibility of porcine CD47 against human SIRPα contributes to the rejection of xenogeneic target cells by macrophages. Neutrophils are an early responder cell that infiltrates xenogeneic grafts. It has also been reported that neutrophil extracellular traps (NETs) activate macrophages as damage-associated pattern molecules (DAMPs). In this review, we summarize recent insights into innate cellular xenogeneic rejection.

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“…Indeed, neutrophils are activated by pro‐inflammatory cytokines (PMID: 2544300, PMID: 1985637, and PMID: 7601250). To minimize the contribution of neutrophils to graft rejection, Wang et al expressed a neutrophil inhibitory protein in pig cells and evaluated cell survival when cocultured with human neutrophils . Cluster of differentiation 31 (CD31) is a surface transmembrane protein widely expressed on endothelial cells, platelets, and leukocytes.…”

Section: Basic Researchmentioning

confidence: 99%

Xenotransplantation literature update, September/October 2018

Taylor

Levy

Burlak

2018

Xenotransplantation

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Damage from hypoxia is a significant hurdle for effect islet transplantation. Past studies have shown that porcine islet cells are protected from hypoxic damage when cultured with human mesenchymal stem cells (MSCs). To better understand how MSCs protect islet cells, Nie et al evaluated the contribution of MSC-secreted factors. MSC-conditioned media (CM) and exosomes reduced cellular apoptosis leading to enhanced cell survival. 1 Additionally, CM and exosomes activated transcriptional programs in islet cells associated with hypoxia tolerance, including hypoxia-inducible factor 1 alpha (Hif1-alpha). The review article by Smith et al 2 focuses on cellular encapsulation to protect recipients from antigenic donor grafts. They discuss new discoveries, issues, and strategies for wrapping up the donor cells, including an overview of device characteristics. 2 of 2 | TAYLOR eT AL. Non-Gal antigens in porcine cells have long been of interest for engineering an optimal porcine donor graft to use in clinical xenotransplantation. The review written by Byrne et al provides detailed and supportive information on a critical non-Gal antigen, B4GalNT2, and illustrates that when deleted, porcine cells are targeted less by the immune system. 10 2 | IMMUNE SUPPRE SS ION Corneal transplants using porcine tissues are a promising solution to a global need for corneal tissue to correct blindness. Descemet's membrane endothelial keratoplasty (DMEK) is an innovative transplantation technique that benefits from low rejection rates and requisite immunosuppression and results in superior vision recovery compared to other surgical techniques. Indeed, in current issue, Kim et al 11 demonstrate that immunosuppression with the common agent tacrolimus can lead to asymptomatic thrombotic microangiopathy that can lead to a number of problems including organ damage. Minimizing the need for immunosuppression by improved graft quality, genetics, and preparation may therefore enhance tissue survival long term. Liu et al 12 tested the feasibility of porcine xenografts using the DMEK technique. Here, the group used two techniques, mechanical stripping and liquid bubble, to prepare the ultra-thin DMEK prior to transplantation. The data, including a comparison of endothelial growth, were promising and indicate that corneal xenografts using DMEK are a viable future option. The authors plan next to test the xeno-DMEK in a non-human primate model. Successful xenotransplantation currently requires immunosuppression. Unfortunately, the immunosuppression regimen may be lethal, by a yet unidentified mechanism, though often linked with anti-CD154 antibody treatment. Ock et al 13 used a non-human primate model (cynomolgus macaques) to evaluate the transcriptional changes prior to and after the standard immunosuppression protocol for porcine cardiac xenotransplantation (alpha-1,3-galactosyltransferase KO pigs). The regimen included cobra venom factor, anti-thymocyte globulin, and rituximab, in the presence or absence of anti-CD154 antibodies. The authors identified a...

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Human CD31 on porcine cells suppress xenogeneic neutrophil‐mediated cytotoxicity via the inhibition of NETosis

Cited by 18 publications

References 60 publications

Inflammatory immune response in recipients of transcatheter aortic valves

Inflammatory immune response in recipients of transcatheter aortic valves

The Innate Cellular Immune Response in Xenotransplantation

Xenotransplantation literature update, September/October 2018

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