| 1. |
- Wang, Hui, et al.
(författare)
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Attenuation of phagocytosis of xenogeneic cells by manipulating CD47.
- 2007
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 109:2, s. 836-42
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Tidskriftsartikel (refereegranskat)abstract
- Signal regulatory protein alpha (SIRPalpha) is a critical immune inhibitory receptor on macrophages, and its interaction with CD47, a ligand for SIRPalpha, prevents autologous phagocytosis. We hypothesized that interspecies incompatibility of CD47 may contribute to the rejection of xenogeneic cells by macrophages. Here, we show that pig CD47 does not interact with mouse SIPRalpha. Similar to CD47-/- mouse cells, porcine red blood cells (RBCs) failed to induce SIRPalpha tyrosine phosphorylation in mouse macrophages. Blocking SIRPalpha with antimouse SIRPalpha mAb (P84) significantly enhanced the phagocytosis of CD47+/+ mouse cells, but did not affect the engulfment of porcine or CD47-/- mouse cells by mouse macrophages. CD47-deficient mice, whose macrophages do not phagocytose CD47-/- mouse cells, showed markedly delayed clearance of porcine RBCs compared with wild-type mouse recipients. Furthermore, mouse CD47 expression on porcine cells markedly reduced their phagocytosis by mouse macrophages both in vitro and in vivo. These results indicate that interspecies incompatibility of CD47 contributes significantly to phagocytosis of xenogeneic cells by macrophages and suggest that genetic manipulation of donor CD47 to improve its interaction with the recipient SIRPalpha may provide a novel approach to prevent phagocyte-mediated xenograft rejection.
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| 2. |
- Wang, Hui, et al.
(författare)
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Lack of CD47 on nonhematopoietic cells induces split macrophage tolerance to CD47null cells
- 2007
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National academy of sciences. - 0027-8424 .- 1091-6490. ; 104:34, s. 13744-13749
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages recognize CD47 as a marker of "self" and phagocytose CD47null hematopoietic cells. Using CD47 chimera models, here, we show that the phagocytic activity of macrophages against CD47null hematopoietic cells is conferred by CD47 expression on nonhematopoietic cells, and this "education" process is hematopoietic cell-independent. Macrophages in the chimeras where nonhematopoietic cells express CD47 phagocytose CD47null cells, whereas those in the chimeras lacking CD47 on nonhematopoietic cells are tolerant to CD47null cells. However, macrophages in the latter chimeras retain phagocytic activity against CD47null RBCs, demonstrating a split macrophage tolerance to CD47null hematopoietic cells. The findings highlight the potential importance of nonhematopoietic cells in the regulation of macrophage function, and suggest a previously uncharacterized mechanism of macrophage tolerance.
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