The BALB/c-specific polymorphic SIRPA enhances its affinity for human CD47, inhibiting phagocytosis against human cells to promote xenogeneic engraftment

被引:39
作者
Iwamoto, Chika [1 ]
Takenaka, Katsuto [1 ]
Urata, Shingo [1 ]
Yamauchi, Takuji [1 ]
Shima, Takahiro [1 ]
Kuriyama, Takuro [1 ]
Daitoku, Shinya [1 ]
Saito, Yasuyuki [2 ]
Miyamoto, Toshihiro [1 ]
Iwasaki, Hiromi [1 ]
Kitabayashi, Issay [3 ]
Itoh, Katsuhiko [4 ]
Kishimoto, Junji [5 ]
Kohda, Daisuke [6 ]
Matozaki, Takashi [2 ,7 ]
Akashi, Koichi [1 ]
机构
[1] Kyushu Univ, Grad Sch Med Sci, Dept Med & Biosyst Sci, Fukuoka 8128582, Japan
[2] Gunma Univ, Lab Biosignal Sci, Inst Mol & Cellular Regulat, Gunma, Japan
[3] Natl Canc Ctr, Div Hematol Malignancy, Tokyo, Japan
[4] Kyoto Univ, Fac Med, Dept Clin Mol Biol, Kyoto, Japan
[5] Kyushu Univ, Digital Med Initiat, Fukuoka 812, Japan
[6] Kyushu Univ, Med Inst Bioregulat, Div Struct Biol, Fukuoka 812, Japan
[7] Kobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Mol & Cellular Signaling, Kobe, Hyogo 657, Japan
关键词
HUMAN HEMATOPOIETIC-CELLS; REGULATORY-PROTEIN-ALPHA; STEM-CELLS; RADIORESISTANT MODEL; MICE; MOUSE; LEUKEMIA; BINDING; MACROPHAGES; ENGULFMENT;
D O I
10.1016/j.exphem.2013.11.005
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
It has been shown that in xenotransplantation of human cells into immunodeficient mice, the mouse strain background is critical. For example, the nonobese diabetic (NOD) strain is most efficient, the BALB/c is moderate, and the C57BL/6 is inefficient for human cell engraftment. We have shown that the NOD-specific polymorphism of the signal regulatory protein-alpha (Sirpa) allows NOD SIRPA to bind human CD47, and the resultant "don't eat me" signaling by this binding prevents host macrophages to engulf human grafts, thereby inhibiting rejection. Here we tested whether the efficient xenotransplantation capability of the BALB/c strain is also mediated by the SIRPA-CD47 self-recognition system. BALB/c SIRPA was capable of binding to human CD47 at an intermediate level between those of C57BL/6 SIRPA and NOD SIRPA. Consistent with its binding activity, BALB/c-derived macrophages exhibited a moderate inhibitory effect on human long-term culture-initiating cells in in vitro cultures, and showed moderate phagocytic activity against human hematopoietic stem cells. The increased affinity of BALB/c SIRPA for human CD47 was mounted at least through the BALB/c-specific L29V SNP within the IgV domain. Thus, the mouse strain effect on xenogeneic engraftment might be ascribed mainly to the binding affinity of strain-specific polymorphic SIRPA with human CD47. This information should be useful for developing a novel immunodeficient strain with superior efficiency for xenogeneic transplantation of human cells. (C) 2014 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
引用
收藏
页码:163 / 171
页数:9
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