Expression of recipient CD47 on rat insulinoma cell xenografts prevents macrophage-mediated rejection through SIRPα inhibitory signaling in mice.
Expression of recipient CD47 on rat insulinoma cell xenografts prevents macrophage-mediated rejection through SIRPα inhibitory signaling in mice.
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DOI：
10.1371/journal.pone.0058359
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ohdan H
中科院分区：
文献类型：
--
作者：
Teraoka Y;Ide K;Morimoto H;Tahara H;Ohdan H
我们之前已经证明CD47的种间不相容是宿主巨噬细胞体外吞噬异种细胞的原因。在本研究中，我们利用体内模型研究了在大鼠胰岛素瘤细胞（INS-1E）中基因工程表达小鼠CD47是否能抑制巨噬细胞介导的异种移植排斥反应。转染pRc/CMV-mouse CD47载体（mCD47-INS-1E）的INS-1E细胞在体外诱导小鼠巨噬细胞sirp α-酪氨酸磷酸化，而转染对照载体（con -INS-1E）的细胞则没有磷酸化。将这些细胞注射到链脲霉素诱导的缺乏T、B和NK细胞的糖尿病Rag2−/−γ链−/−小鼠腹腔，小鼠CD47在INS-1E细胞上的表达显著降低了这些细胞对巨噬细胞吞噬的敏感性。此外，这些小鼠在接受mCD47-INS-1E后血糖正常，而接受con - ins - 1e的小鼠未能达到正常血糖。此外，向mCD47-INS-1E细胞小鼠受体注射抗小鼠SIRPα阻断单克隆抗体可阻止正常血糖的实现。这些结果表明，CD47的种间不相容性显著促进了巨噬细胞对异种细胞的体内排斥反应。因此，基因诱导受体CD47在异种供体细胞上的表达可通过SIPRα向受体巨噬细胞提供抑制信号；这构成了一种预防巨噬细胞介导的异种移植排斥反应的新方法。
We have previously proven that the interspecies incompatibility of CD47 is responsible for in vitro phagocytosis of xenogeneic cells by host macrophages. Utilizing an in vivo model in the present study, we investigated whether genetically engineered expression of mouse CD47 in rat insulinoma cells (INS-1E) could inhibit macrophage-mediated xenograft rejection. INS-1E cells transfected with the pRc/CMV-mouse CD47 vector (mCD47-INS-1E) induced SIRPα-tyrosine phosphorylation in mouse macrophages in vitro, whereas cells transfected with the control vector (cont-INS-1E) did not. When these cells were injected into the peritoneal cavity of streptozotocin-induced diabetic Rag2−/−γ chain −/− mice, which lack T, B, and NK cells, the expression of mouse CD47 on the INS-1E cells markedly reduced the susceptibility of these cells to phagocytosis by macrophages. Moreover, these mice became normoglycemic after receiving mCD47-INS-1E, whereas the mice that received cont-INS-1E failed to achieve normoglycemia. Furthermore, injection of an anti-mouse SIRPα blocking monoclonal antibody into the mouse recipients of mCD47-INS-1E cells prevented achievement of normoglycemia. These results demonstrate that interspecies incompatibility of CD47 significantly contributes to in vivo rejection of xenogeneic cells by macrophages. Thus, genetic induction of the expression of recipient CD47 on xenogeneic donor cells could provide inhibitory signals to recipient macrophages via SIPRα; this constitutes a novel approach for preventing macrophage-mediated xenograft rejection.
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影响因子：
82.9
作者：
Yamada, K;Yazawa, K;Sachs, DH
通讯作者：
Sachs, DH
DOI：
10.1073/pnas.0609661104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Ide, Kentaro;Wang, Hui;Ohdan, Hideki
通讯作者：
Ohdan, Hideki
影响因子：
20.3
作者：
Wang, Hui;VerHalen, Jon;Yang, Yong-Guang
通讯作者：
Yang, Yong-Guang
DOI：
10.1083/jcb.200708043
发表时间：
2008-03-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Tsai RK;Discher DE
通讯作者：
Discher DE
影响因子：
4.8
作者：
Jiang, PH;Lagenaur, CF;Narayanan, V
通讯作者：
Narayanan, V