Human CD200 suppresses macrophage-mediated xenogeneic cytotoxicity and phagocytosis

Purpose Various strategies, such as the generation of alpha-1,3-galactosyltransferase knocked-out pigs and CD55 transgenic pigs, have been investigated to inhibit pig to human xenogeneic rejection. Our aim is to develop strategies to overcome the hurdle of not only hyper acute rejection, but also th...

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Veröffentlicht in:Surgery today (Tokyo, Japan) Japan), 2018, Vol.48 (1), p.119-126
Hauptverfasser: Sakai, Rieko, Maeda, Akira, Choi, Thuy-Vy, Lo, Pei-Chi, Jiaravuthisan, Patmika, Shabri, Afifah Mod, Wang, Han-Tang, Matsuura, Rei, Kodama, Tasuku, Eguchi, Hiroshi, Okuyama, Hiroomi, Miyagawa, Shuji
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container_end_page 126
container_issue 1
container_start_page 119
container_title Surgery today (Tokyo, Japan)
container_volume 48
creator Sakai, Rieko
Maeda, Akira
Choi, Thuy-Vy
Lo, Pei-Chi
Jiaravuthisan, Patmika
Shabri, Afifah Mod
Wang, Han-Tang
Matsuura, Rei
Kodama, Tasuku
Eguchi, Hiroshi
Okuyama, Hiroomi
Miyagawa, Shuji
description Purpose Various strategies, such as the generation of alpha-1,3-galactosyltransferase knocked-out pigs and CD55 transgenic pigs, have been investigated to inhibit pig to human xenogeneic rejection. Our aim is to develop strategies to overcome the hurdle of not only hyper acute rejection, but also that of cellular xenogeneic rejection (CXR). Although macrophages have been well known to play a critical role in CXR, monocyte/macrophage-mediated xenogeneic rejection has not been well studied. In this study, we evaluated the effect of CD200 in xenogeneic rejection by macrophages. Methods Naïve swine endothelial cells (SEC) and SEC/CD200 were co-cultured with M0 macrophages and the cytotoxicity was measured by a WST-8 assay. The phagocytosis of SEC and SEC/CD200 by macrophages was analyzed by flow cytometry. Results While CD200 failed to suppress a significant amount of cytotoxicity against SEC by monocytes, M0 macrophage-mediated cytotoxicity was significantly suppressed by human CD200. The phagocytosis by M0 macrophages was also tested. The phagocytosis assay revealed that human CD200 suppresses M0 macrophage-mediated phagocytosis. Conclusions Our findings indicate that human CD200 suppresses the xenogeneic rejection by CD200R + macrophages and that the generation of hCD200 transgenic pigs for use in xenografts is very attractive for preventing the macrophage-mediated rejection.
doi_str_mv 10.1007/s00595-017-1546-2
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Our aim is to develop strategies to overcome the hurdle of not only hyper acute rejection, but also that of cellular xenogeneic rejection (CXR). Although macrophages have been well known to play a critical role in CXR, monocyte/macrophage-mediated xenogeneic rejection has not been well studied. In this study, we evaluated the effect of CD200 in xenogeneic rejection by macrophages. Methods Naïve swine endothelial cells (SEC) and SEC/CD200 were co-cultured with M0 macrophages and the cytotoxicity was measured by a WST-8 assay. The phagocytosis of SEC and SEC/CD200 by macrophages was analyzed by flow cytometry. Results While CD200 failed to suppress a significant amount of cytotoxicity against SEC by monocytes, M0 macrophage-mediated cytotoxicity was significantly suppressed by human CD200. The phagocytosis by M0 macrophages was also tested. The phagocytosis assay revealed that human CD200 suppresses M0 macrophage-mediated phagocytosis. Conclusions Our findings indicate that human CD200 suppresses the xenogeneic rejection by CD200R + macrophages and that the generation of hCD200 transgenic pigs for use in xenografts is very attractive for preventing the macrophage-mediated rejection.</description><identifier>ISSN: 0941-1291</identifier><identifier>EISSN: 1436-2813</identifier><identifier>DOI: 10.1007/s00595-017-1546-2</identifier><identifier>PMID: 28573328</identifier><language>eng</language><publisher>Tokyo: Springer Japan</publisher><subject>Animals ; Antigens, CD - physiology ; Cells, Cultured ; Cytotoxicity, Immunologic - genetics ; Endothelial Cells - immunology ; Flow Cytometry ; Graft Rejection - genetics ; Graft Rejection - immunology ; Humans ; Macrophages - immunology ; Medicine ; Medicine &amp; Public Health ; Original Article ; Phagocytosis - genetics ; Surgery ; Surgical Oncology ; Swine</subject><ispartof>Surgery today (Tokyo, Japan), 2018, Vol.48 (1), p.119-126</ispartof><rights>Springer Japan 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-p184t-3017bc1b63ef78c8ee33126cdbfb28b0f968f7b2033a9d207bca5f3bf73cddbe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00595-017-1546-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00595-017-1546-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28573328$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sakai, Rieko</creatorcontrib><creatorcontrib>Maeda, Akira</creatorcontrib><creatorcontrib>Choi, Thuy-Vy</creatorcontrib><creatorcontrib>Lo, Pei-Chi</creatorcontrib><creatorcontrib>Jiaravuthisan, Patmika</creatorcontrib><creatorcontrib>Shabri, Afifah Mod</creatorcontrib><creatorcontrib>Wang, Han-Tang</creatorcontrib><creatorcontrib>Matsuura, Rei</creatorcontrib><creatorcontrib>Kodama, Tasuku</creatorcontrib><creatorcontrib>Eguchi, Hiroshi</creatorcontrib><creatorcontrib>Okuyama, Hiroomi</creatorcontrib><creatorcontrib>Miyagawa, Shuji</creatorcontrib><title>Human CD200 suppresses macrophage-mediated xenogeneic cytotoxicity and phagocytosis</title><title>Surgery today (Tokyo, Japan)</title><addtitle>Surg Today</addtitle><addtitle>Surg Today</addtitle><description>Purpose Various strategies, such as the generation of alpha-1,3-galactosyltransferase knocked-out pigs and CD55 transgenic pigs, have been investigated to inhibit pig to human xenogeneic rejection. Our aim is to develop strategies to overcome the hurdle of not only hyper acute rejection, but also that of cellular xenogeneic rejection (CXR). Although macrophages have been well known to play a critical role in CXR, monocyte/macrophage-mediated xenogeneic rejection has not been well studied. In this study, we evaluated the effect of CD200 in xenogeneic rejection by macrophages. Methods Naïve swine endothelial cells (SEC) and SEC/CD200 were co-cultured with M0 macrophages and the cytotoxicity was measured by a WST-8 assay. The phagocytosis of SEC and SEC/CD200 by macrophages was analyzed by flow cytometry. Results While CD200 failed to suppress a significant amount of cytotoxicity against SEC by monocytes, M0 macrophage-mediated cytotoxicity was significantly suppressed by human CD200. The phagocytosis by M0 macrophages was also tested. The phagocytosis assay revealed that human CD200 suppresses M0 macrophage-mediated phagocytosis. 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Our aim is to develop strategies to overcome the hurdle of not only hyper acute rejection, but also that of cellular xenogeneic rejection (CXR). Although macrophages have been well known to play a critical role in CXR, monocyte/macrophage-mediated xenogeneic rejection has not been well studied. In this study, we evaluated the effect of CD200 in xenogeneic rejection by macrophages. Methods Naïve swine endothelial cells (SEC) and SEC/CD200 were co-cultured with M0 macrophages and the cytotoxicity was measured by a WST-8 assay. The phagocytosis of SEC and SEC/CD200 by macrophages was analyzed by flow cytometry. Results While CD200 failed to suppress a significant amount of cytotoxicity against SEC by monocytes, M0 macrophage-mediated cytotoxicity was significantly suppressed by human CD200. The phagocytosis by M0 macrophages was also tested. The phagocytosis assay revealed that human CD200 suppresses M0 macrophage-mediated phagocytosis. 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subjects Animals
Antigens, CD - physiology
Cells, Cultured
Cytotoxicity, Immunologic - genetics
Endothelial Cells - immunology
Flow Cytometry
Graft Rejection - genetics
Graft Rejection - immunology
Humans
Macrophages - immunology
Medicine
Medicine & Public Health
Original Article
Phagocytosis - genetics
Surgery
Surgical Oncology
Swine
title Human CD200 suppresses macrophage-mediated xenogeneic cytotoxicity and phagocytosis
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