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別タイトル
異種移植におけるマクロファージ性拒絶抑制効果に対するレシピエント種CD47遺伝子導入の有用性
著者
寺岡 義布史
NDC
医学
抄録(英)
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 SIRPa-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 SIRPa 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 SIPRa; this constitutes a novel approach for preventing macrophage-mediated xenograft rejection.
作成年月日
2014-11-21
言語
英語
NII資源タイプ
学位論文
広大資料タイプ
学位論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
ETD
権利情報
Copyright(c) by Author
関連情報(references)
Yoshifumi Teraoka, Kentaro Ide, Hiroshi Morimoto, Hiroyuki Tahara, Hideki Ohdan; Expression of Recipient CD47 on Rat Insulinoma Cell Xenografts Prevents Macrophage-Mediated Rejection through SIRPα Inhibitory Signaling in Mice; PLoS ONE; March 2013, Volume 8 Issue 3, e58359 (doi: 10.1371/journal.pone.0058359)
関連情報URL(references)
http://dx.doi.org/10.1371/journal.pone.0058359
学位記番号
甲第6197号
授与大学
広島大学(Hiroshima University)
学位名
博士(医学)
学位名の英名
Philosophy in Medical Science
学位の種類の英名
doctoral
学位授与年月日
2013-05-23
部局名
医歯薬学総合研究科