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Suppression of human macrophages by human CD200 and human CD47 during xenogeneic immune response
이종 면역반응에서 인간 CD200과 CD47의 대식세포 억제능 연구

DC Field Value Language
dc.contributor.advisor안규리-
dc.contributor.author강보혜-
dc.date.accessioned2017-10-31T08:24:49Z-
dc.date.available2020-03-02T02:42:16Z-
dc.date.issued2017-08-
dc.identifier.other000000145318-
dc.identifier.urihttps://hdl.handle.net/10371/137994-
dc.description학위논문 (석사)-- 서울대학교 대학원 의과대학 의학과, 2017. 8. 안규리.-
dc.description.abstractBackground: CD200 and CD47 are inhibitory proteins expressed on a variety of cells and they bind to their receptors to exert inhibitory functions. CD47 suppresses the phagocytic activity of macrophages through SIRPα ligation and CD200-CD200R interaction induces the intracellular signaling of CD200R and promotes immune modulation such as suppression of cell adhesion and cytokine release, thus enhancing engraftment and immune tolerance. The aim of this study is to compare the suppressive activity of human CD200 and human CD47 against human macrophages and assess the additive effects of both molecules in the interaction of porcine endothelial cells (PECs) and human macrophages.
Materials and Methods: Porcine endothelial cell lines that stably overexpress human CD200 or CD47 were established by human CD200 or CD47 containing recombinant lentivirus construction followed by viral transduction. Human macrophages were incubated with recombinant PECs to evaluate suppressive effect of human CD200 and CD47 on cytotoxicity, phagocytosis, secretion of pro-inflammatory cytokines and proliferation of human macrophages during in the xenogeneic immune reaction.
Results: The present study demonstrated that overexpression of both human CD200 and human CD47 in PECs suppressed the xenogeneic immune response of human macrophages. Human CD200 and CD47 inhibited cytotoxicity such as cell necrosis and early and late apoptosis and suppressed phagocytosis of human macrophages. Also, human CD200 and CD47 negatively controlled pro-inflammatory cytokine secretion and proliferation of human macrophages in response to xenogeneic stimulation. Furthermore, the co-expression of human CD200 and human CD47 had additive effects in suppressing macrophage activation in response to xenogeneic stimulation.
Conclusion: both human CD200 and human CD47 suppressed the activation of human macrophages in response to xenogeneic stimulation. Moreover, the suppressive activity of the co-expression of human CD200 and human CD47 was more effective against macrophage activation than that of the expression of either CD200 or CD47 alone. Therefore, the generation of double-transgenic pigs with human CD200 and human CD47 could be a promising approach for improving xenograft survival.
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dc.description.tableofcontents1. Introduction 1
2. Materials and Methods 7
(1) Target gene preparation 7
(2) Recombinant lentivirus production 8
(3) Viral transduction 8
(4) Human macrophage preparation 12
(5) Cell culture 12
(6) Cytotoxicity assay 13
(7) Phagocytic assay 13
(8) Cytokine assay 14
(9) Proliferation assay 14
(10) Statistics 14
3. Results 15
(1) Sequence similarity between CD200 and CD47 of human and porcine 15
(2) Expression of transmembrane and secretory form of human CD200 in PECs 17
(3) Expression of transmembrane and secretory forms of human CD47 in PECs 18
(4) Co-expression of human CD200 and human CD47 in PECs 18
(5) CD14 expression in human macrophages prepared from PBMCs 21
(6) Suppression of the cytotoxicity of human macrophages by overexpression of human CD200 and human CD47 in PECs 22
(7) Suppression of the phagocytic activity of human macrophages by ㅐver-expression of human CD200 and human CD47 in PECs 25
(8) Inhibition of pro-inflammatory cytokine secretion from human macrophages by human CD200 and human CD47 in PECs 27
(9) Suppression of the proliferation of human macrophages by human CD200 and human CD47 in PECs 30
(10) Additive effects of human CD200 and human CD47 on the cytotoxic activity of human macrophages against PECs 32
(11) Suppression of the phagocytic activity of human macrophages by co-expression of human CD200 and human CD47 35
(12) Comparison of the cytokine suppressive potency between single- and co-expression of human CD200 and human CD47 37
(13) Suppression of the proliferation of human macrophages by co-expression of human CD200 and human CD47 40
4. Discussion 43
5. References 46
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dc.formatapplication/pdf-
dc.format.extent797585 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subjectXenotransplant-
dc.subjectMacrophage-
dc.subjectCD200-
dc.subjectCD47-
dc.subjectporcine-
dc.subject.ddcXenotransplantation, Suppression, CD200, CD47-
dc.titleSuppression of human macrophages by human CD200 and human CD47 during xenogeneic immune response-
dc.title.alternative이종 면역반응에서 인간 CD200과 CD47의 대식세포 억제능 연구-
dc.typeThesis-
dc.description.degreeMaster-
dc.contributor.affiliation의과대학 의학과-
dc.date.awarded2017-08-
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Master's Degree_의학과)
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