异种移植
巨噬细胞
吞噬作用
细胞毒性
分子生物学
流式细胞术
先天免疫系统
磷酸化
免疫系统
化学
细胞因子
生物
免疫学
体外
细胞生物学
移植
医学
生物化学
内科学
作者
Shuhei Kogata,Pei‐Chi Lo,Akira Maeda,Chizu Okamatsu,Kazuki Sato,Riho Yamamoto,Tomoko Haneda,Tomohisa Yoneyama,Chiyoshi Toyama,Hiroshi Eguchi,Kazunori Masahata,Masafumi Kamiyama,Hiroomi Okuyama,Shuji Miyagawa
标识
DOI:10.1016/j.trim.2022.101663
摘要
Cellular xenogeneic rejection by the innate immune system is a major immunological obstruction that needs to be overcome for the successful clinical use of xenografts. Our focus has been on macrophage-mediated xenogeneic rejection, since suppressing macrophage function has considerable potential for practical applications in the area of xenotransplantation. We report herein on an investigation of the suppressive effect of human CD177 (hCD177) against macrophage-mediated xenogeneic rejection. Wild type swine aortic endothelial cell (SEC) and an SEC transfectant with hCD177 (SEC/hCD177) were co-cultured with macrophages, and the degree of cytotoxicity was evaluated by WST-8 assays, and phagocytosis was examined using Calcein-AM labeling methods. The expression of anti/pro-inflammatory cytokines was evaluated by RT-qPCR and the phosphorylation of SHP-1 on macrophages in co-culture was evaluated by Western blotting. The result of cytotoxicity assays indicated that hCD177 suppressed M1 macrophage-mediated xenogeneic rejection (vs. SEC, p < 0.0001). Similarly, the result of phagocytosis assays indicated that hCD177 suppressed it (vs. SEC, p < 0.05). In addition, hCD177 significantly suppressed the expression of IL-1β, a pro-inflammatory cytokine, in M1 macrophages (vs. SEC, p < 0.01). Luciferase assays using THP1-Lucia NF-kB also showed a significant difference in NF-kB activation (vs. SEC, p < 0.001). In addition, hCD177 was found to induce the phosphorylation of SHP-1 in M1 macrophages (vs. SEC, p < 0.05). These findings indicate that hCD177 suppresses M1 macrophage-mediated xenogeneic rejection, at least in part via in the phosphorylation of SHP-1.
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