Suppression of macrophage-mediated xenogeneic rejection by the ectopic expression of human CD177

被引：7

作者：

Kogata, Shuhei ^{[1
,2
]}

Lo, Pei -Chi ^{[1
]}

Maeda, Akira ^{[1
,4
]}

Okamatsu, Chizu ^{[1
]}

Sato, Kazuki ^{[1
]}

Yamamoto, Riho ^{[1
]}

Haneda, Tomoko ^{[1
]}

Yoneyama, Tomohisa ^{[1
]}

Toyama, Chiyoshi ^{[1
]}

Eguchi, Hiroshi ^{[1
]}

Masahata, Kazunori ^{[1
]}

Kamiyama, Masafumi ^{[1
]}

Okuyama, Hiroomi ^{[1
]}

Miyagawa, Shuji ^{[1
,3
]}

机构：

[1] Osaka Univ, Dept Pediat Surg, Grad Sch Med, Osaka, Japan

[2] Kindai Univ, Dept Surg, Div Pediat Surg, Fac Med, Osaka, Japan

[3] Meiji Univ, Int Inst Bioresource Res, Kanagawa, Japan

[4] Osaka Univ, Dept Surg, Grad Sch Med, 2-2 Yamada Oka, Suita, Osaka, Japan

来源：

TRANSPLANT IMMUNOLOGY | 2022年 / 74卷

关键词：

Human CD31; Human CD177; Macrophage; Xenogeneic rejection; Xenotransplantation; CD46 TRANSGENIC PIG; INFLAMMASOMES MECHANISM; CYTOTOXICITY; ADHESION; PROTEIN; ACTIVATION; RECEPTOR; CELLS; INHIBITION; PROTECTION;

D O I：

10.1016/j.trim.2022.101663

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

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 xeno-geneic 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 cyto-toxicity 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-1 beta, 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.

引用

页数：12

共 54 条

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