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ID 20739
file
creator
Ide, Kentaro
Wang, Hui
Tahara, Hiroyuki
Liu, Jianxiang
Wang, Xiaoying
Sykes, Megan
Yang, Yong-Guang
subject
xenotransplantation
phagocytosis
reticuloendothelial system
NDC
Medical sciences
abstract
We have previously proven that human macrophages can phagocytose porcine cells even in the absence of Ab or complement opsonization, indicating that macrophages present a pivotal immunological obstacle to xenotransplantation. A recent report indicates that the signal regulatory protein (SIRP)α is a critical immune inhibitory receptor on macrophages, and its interaction with CD47, a ligand for SIRPα, prevents autologous phagocytosis. Considering the limited compatibility (73%) in amino acid sequences between pig and human CD47, we hypothesized that the interspecies incompatibility of CD47 may contribute to the rejection of xenogeneic cells by macrophages. In the present study, we have demonstrated that porcine CD47 does not induce SIRPα tyrosine phosphorylation in human macrophage-like cell line, and soluble human CD47-Fc fusion protein inhibits the phagocytic activity of human macrophages toward porcine cells. In addition, we have verified that manipulation of porcine cells for expression of human CD47 radically reduces the susceptibility of the cells to phagocytosis by human macrophages. These results indicate that the interspecies incompatibility of CD47 significantly contributes to the rejection of xenogeneic cells by macrophages. Genetic induction of human CD47 on porcine cells could provide inhibitory signaling to SIRPα on human macrophages, providing a novel approach to preventing macrophage-mediated xenograft rejection.
journal title
Proceedings of the National Academy of Sciences of the United States of America
volume
Volume 104
issue
Issue 12
start page
5062
end page
5066
date of issued
2007-03-20
publisher
National Academy of Sciences
issn
0027-8424
ncid
publisher doi
pubmed id
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
author
rights
Copyright (c) 2007 the National Academy of Sciences
relation url
department
Graduate School of Biomedical Science