The immunosuppressant Protosappanin A diminished recipient T cell migration into allograft via inhibition of IP-10 in rat heart transplant.
The immunosuppressant Protosappanin A diminished recipient T cell migration into allograft via inhibition of IP-10 in rat heart transplant.
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免疫抑制剂原苏木素 A 通过抑制大鼠心脏移植中的 IP-10 减少受体 T 细胞向同种异体移植物的迁移
DOI：
10.1371/journal.pone.0096138
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yu B
中科院分区：
文献类型：
--
作者：
Zhang M;He J;Hou J;Wu J;Sun M;Cui J;Tian J;Jiang M;Yu B
免疫抑制剂原皂素A （prosappanin A, PrA）可促进同种异体心脏移植物存活，减少炎症细胞浸润，抑制干扰素γ诱导蛋白10kda (IP-10) mRNA表达。趋化因子IP-10与其同源受体CXCR3的结合在同种异体移植物免疫中起着至关重要的作用，特别是通过介导效应T细胞向同种异体移植物组织的募集。在这项研究中，我们试图在大鼠模型中确定普拉介导的IP-10抑制是否有助于减少T细胞浸润到同种异体心脏移植中的作用。心脏移植术后灌胃给予PrA (25 mg/kg / d)，可显著降低同种异体移植物中IP-10 mRNA水平的升高，并可阻止移植后7 d受体大鼠外周血单个核细胞（PBMC）分泌IP-10。此外，体外实验表明，添加PrA控制PBMC可阻止IP-10的分泌。趋化迁移试验用于评估受体T细胞向PBMC上清的迁移。给药后，PBMC上清液诱导的T细胞迁移受损。另外的体外实验显示，PrA略微减少naïve T细胞向趋化因子的迁移。PBMC上清液中IP-10的存在阻止了PrA减少T细胞在PrA处理受体中的迁移。CXCR3趋化因子配体Mig和非CXCR3趋化因子配体SDF-1对pra处理受体的T细胞迁移没有任何影响。抗cxcr3抗体的加入恢复了pra介导的T细胞迁移抑制。免疫荧光显微镜显示IP-10主要在CD68阳性浸润单核细胞中表达。此外，PrA持续减少CXCR3+T细胞在同种异体心脏移植物中的浸润。在PrA处理的同种异体移植物中，CXCR3染色强度的降低有助于先前PrA诱导的naïve T细胞迁移活性的抑制。综上所述，这些数据表明，PrA对IP-10活性的抑制减少了受体T细胞在同种异体心脏移植物中的迁移和浸润，从而部分解释了PrA的免疫抑制作用。
The immunosuppressant Protosappanin A (PrA), isolated from the medicinal herb, promotes cardiac allograft survival, diminishes inflammatory cell infiltration, and inhibits interferon γ-induced protein 10 kDa (IP-10) mRNA expression in rats cardiac grafts. Binding of the chemokine IP-10 to its cognate receptor, CXCR3, plays crucial roles in allograft immunity, especially by mediating the recruitment of effector T cells to allografted tissues. In this study, we attempted to determine whether PrA-mediated inhibition of IP-10 contributes to the effect of reduced T cell infiltration into cardiac allograft within a rat model. Administration of PrA (25 mg/kg daily) via oral gavage following heart transplantation significantly reduced the increase of IP-10 mRNA level in allograft and prevented IP-10 secretion by peripheral blood mononuclear cells (PBMC) isolated from recipient rats seven days posttransplantation. Furthermore, in vitro experiments demonstrated that PrA addition to control PBMC prevented IP-10 secretion. Chemotactic migration assays were utilized to evaluate recipient T cell migration towards PBMC supernatant. PrA administration impaired PBMC supernatant-induced T cell migration. Additional in vitro experiments revealed that PrA slightly reduced naïve T cell migration towards chemokines. The presence of IP-10 in PBMC supernatant prevented PrA from reducing T cell migration in PrA-treated recipients. Neither CXCR3 chemokine ligand Mig nor non-CXCR3 chemokine ligand SDF-1 had any effect on T cell migration in PrA-treated recipients. The addition of anti-CXCR3 antibody restored PrA-mediated inhibition of T cell migration. Immunofluorescence microscopy showed that IP-10 was expressed mainly in CD68 positive infiltrating monocytes. Furthermore, PrA consistently reduced CXCR3+T cell infiltration into cardiac allografts. The reduced intensity of CXCR3 staining in PrA-treated allografts contributed to the previously depressed naïve T cell migrating activity induced by PrA. Collectively, these data indicate that PrA inhibition of IP-10 activity reduced recipient T cell migration and infiltration of cardiac allografts, thus partially explaining the immunosuppressive effect of PrA.
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影响因子：
2.7
作者：
Liu, Ai-Lin;Shu, Shi-Hui;Du, Guan-Hua
通讯作者：
Du, Guan-Hua
影响因子：
6.2
作者：
Crescioli, Clara;Buonamano, Andrea;Maccherini, Massinio
通讯作者：
Maccherini, Massinio
影响因子：
0.9
作者：
Wu, J.;Hou, J. B.;Yu, B.
通讯作者：
Yu, B.
影响因子：
3.1
作者：
Gomez-Lopez N;Tanaka S;Zaeem Z;Metz GA;Olson DM
通讯作者：
Olson DM
DOI：
10.1016/s0022-5223(19)42744-x
发表时间：
1969-01-01
影响因子：
6
作者：
ONO, K;LINDSEY, ES
通讯作者：
LINDSEY, ES