Volume 9 Issue 3
May  2018
Turn off MathJax
Article Contents
Article Navigation >  ORGAN TRANSPLANTATION  > 2018  >  9(3): 181-187
Zhang Qing, Zhou Cuibing, Wang Chengjun, et al. Study of immunoregulatory effect of sirolimus on xenotransplantaion with arterial patch[J]. ORGAN TRANSPLANTATION, 2018, 9(3): 181-187. doi: 10.3969/j.issn.1674-7445.2018.03.003
Citation: Zhang Qing, Zhou Cuibing, Wang Chengjun, et al. Study of immunoregulatory effect of sirolimus on xenotransplantaion with arterial patch[J]. ORGAN TRANSPLANTATION, 2018, 9(3): 181-187. doi: 10.3969/j.issn.1674-7445.2018.03.003
shu

Study of immunoregulatory effect of sirolimus on xenotransplantaion with arterial patch

doi: 10.3969/j.issn.1674-7445.2018.03.003

  • Sun Yat-sen University, Guangzhou 510275, China

More Information
  • Corresponding author: Mou Lisha, Email: molly__molly@163.com
  • Received Date: 2018-02-10
    Available Online: 2021-01-19
  • Publish Date: 2018-05-15
    Abstract
  •   Objective  To investigate the immunoregulatory effect of sirolimus on the xenotransplantation with arterial patch.  Methods  The xenotransplantation of arterial grafts was taken from the wild-type Bama pigs to cynomolgus monkeys. The peripheral blood mononuclear cells of recipient monkeys at 14 days after xenotransplantation (POD14) were selected as subjects. Dimethyl sulphoxide (DMSO) was used in the control group (volume ratio of 1:1 000) and sirolimus was administered in the sirolimus experimental group (final concentration of 0.1 μmol/L and 0.5 μmol/L). The cells were cultured for 1.0 and 5.5 d, respectively. The activity of POD14 cells was evaluated. The DMSO control and sirolimus experimental groups (final concentration of 0.1 μmol/L) were established and cultured for 5.5 d. The quantity of T and B cells in POD14 cells was counted and the expression levels of cytokines and messenger RNA (mRNA) were quantitatively measured.  Results  Compared with the DMSO control group, the activity of POD14 cells was significantly decreased after sirolimus treatment at a final concentration of 0.1 and 0.5 μmol/L for 1.0 d ( P < 0.01-0.001). After sirolimus treatment at a final concentration of 0.1 and 0.5 μmol/L for 5.5 d, the activity of POD14 cells was significantly decreased (both P < 0.001). Compared with the DMSO control group, the quantity of CD3+CD4+ T cells and CD3+CD8+T cells in POD14 cells was significantly reduced after sirolimus treatment at a final concentration 0.1 μmol/L ( P < 0.05-0.01), whereas the quantity of CD3-CD20+B cells was considerably elevated ( P < 0.01). Compared with DMSO control group, the levels of interferon(IFN)-γ, interleukin(IL)-2, IL-4, IL-5 and IL-6 in the sirolimus experimental group were significantly down-regulated ( P < 0.05-0.001). The expression levels of IFN-γ, tumor necrosis factor(TNF)-α, IL-2, IL-4, IL-5 and IL-6 mRNA were significantly down-regulated ( P < 0.05-0.001).   Conclusions   Sirolimus inhibits the proliferation of POD14 cells in the recipient monkeys after xenotransplantation with arterial patch. The underlying mechanism is that the sirolimus can reduce the quantity of T cells and suppress the expression and secretion of immune rejection-related cytokines.

     

    • FullText(HTML)
  • loading
    • References(23)
  • [1]
    MARTINS PN, TULLIUS SG, MARKMANN JF. Immunosenescence and immune response in organ transplantation[J]. Int Rev Immunol, 2014, 33(3): 162- 173. DOI: 10.3109/08830185.2013.829469.
    [2]
    DE FIJTER JW. Cancer and mTOR inhibitors in transplant recipients[J]. Transplantation, 2017, 101(1):45-55. DOI: 10.1097/TP.0000000000001447.
    [3]
    LIM WH, ERIS J, KANELLIS J, et al. A systematic review of conversion from calcineurin inhibitor to mammalian target of rapamycin inhibitors for maintenance immunosuppression in kidney transplant recipients[J]. Am J Transplant, 2014, 14(9): 2106-2119. DOI: 10.1111/ajt.12795.
    [4]
    赵成江, 叶学军, 陈姣, 等.食蟹猴腹主动脉补丁缝合术后的免疫排斥反应监测[J].器官移植, 2017, 8(2): 127-131. DOI: 10.3969/j.issn.1674-7445.2017.02.007.

    ZHAO CJ, YE XJ, CHEN J, et al. Monitoring of immune rejection after abdominal aortic patch suture in cynomolgus monkeys[J]. Organ Transplant, 2017, 8(2): 127-131. DOI: 10.3969/j.issn.1674-7445.2017.02.007.
    [5]
    COOPER DKC, PIERSON RN 3RD, HERING BJ, et al. Regulation of clinical xenotransplantation-time for a reappraisal[J]. Transplantation, 2017, 101(8): 1766- 1769. DOI: 10.1097/TP.0000000000001683.
    [6]
    PHELPS CJ, KOIKE C, VAUGHT TD, et al. Production of alpha 1, 3-galactosyltransferase-deficient pigs[J]. Science, 2003, 299(5605): 411-414. doi: 10.1126/science.1078942
    [7]
    KWON DN, LEE K, KANG MJ, et al. Production of biallelic CMP-Neu5Ac hydroxylase knock-out pigs[J]. Sci Rep, 2013, 3: 1981. DOI: 10.1038/srep01981.
    [8]
    NIU D, WEI HJ, LIN L, et al. Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9[J]. Science, 2017, 357(6357): 1303-1307. DOI: 10.1126/science.aan4187.
    [9]
    SCOBIE L, DENNER J, SCHUURMAN HJ. Inactivation of porcine endogenous retrovirus in pigs using CRISPRCas9, editorial commentary[J]. Xenotransplantation, 2017, 24(6). DOI: 10.1111/xen.12363.
    [10]
    COOPER DK, HARA H, EZZELARAB M, et al. The potential of genetically-engineered pigs in providing an alternative source of organs and cells for transplantation[J]. J Biomed Res, 2013, 27(4): 249-253. DOI: 10.7555/JBR.27.20130063.
    [11]
    KIM GA, LEE EM, JIN JX, et al. Generation of CMAHKO/GTKO/shTNFRI-Fc/HO-1 quadruple gene modified pigs[J]. Transgenic Res, 2017, 26(4): 435-445. DOI: 10.1007/s11248-017-0021-6.
    [12]
    HOLT CD. Overview of immunosuppressive therapy in solid organ transplantation[J]. Anesthesiol Clin, 2017, 35(3): 365-380. DOI: 10.1016/j.anclin.2017.04.001.
    [13]
    ILYAS M, COLEGIO OR, KAPLAN B, et al. Cutaneous toxicities from transplantation-related medications[J]. Am J Transplant, 2017, 17(11): 2782-2789. DOI: 10.1111/ajt.14337.
    [14]
    EZZELARAB MB, EKSER B, ECHEVERRI G, et al. Costimulation blockade in pig artery patch xenotransplantation - a simple model to monitor the adaptive immune response in nonhuman primates[J]. Xenotransplantation, 2012, 19(4): 221-232. DOI: 10.1111/j.1399-3089.2012.00711.x.
    [15]
    DALLMAN MJ. Cytokines and transplantation: Th1/ Th2 regulation of the immune response to solid organ transplants in the adult[J]. Curr Opin Immunol, 1995, 7(5): 632-638. doi: 10.1016/0952-7915(95)80069-7
    [16]
    NICKERSON P, STEURER W, STEIGER J, et al. Cytokines and the Th1/Th2 paradigm in transplantation[J]. Curr Opin Immunol, 1994, 6(5): 757-764. doi: 10.1016/0952-7915(94)90081-7
    [17]
    ROSSI JF, LU ZY, JOURDAN M, et al. Interleukin-6 as a therapeutic target[J]. Clin Cancer Res, 2015, 21(6): 1248-1257. DOI: 10.1158/1078-0432.CCR-14-2291.
    [18]
    ZHANG W, HE J. Interleukin-6 is a key factor for immunoglobulin-like transcript-4-mediated immune injury in sepsis[J]. J Intensive Care, 2018, 6:22. DOI: 10.1186/s40560-018-0294-8.
    [19]
    CHAE MS, MOON KU, CHUNG HS, et al. Serum interleukin-6 and tumor necrosis factor-α are associated with early graft regeneration after living donor livertransplantation[J]. PLoS One, 2018, 13(4): e0195262. DOI: 10.1371/journal.pone.0195262.
    [20]
    VALPIONE S, PASQUALI S, CAMPANA LG, et al. Sex and interleukin-6 are prognostic factors for autoimmune toxicity following treatment with anti-CTLA4 blockade[J]. J Transl Med, 2018, 16(1): 94. DOI: 10.1186/s12967-018- 1467-x.
    [21]
    G O M E Z - R O D R I G U E Z J, W O H L F E RT E A, HANDON R, et al. Itk-mediated integration of T cell receptor and cytokine signaling regulates the balance between Th17 and regulatory T cells[J]. J Exp Med, 2014, 211(3): 529-543. DOI: 10.1084/jem.20131459.
    [22]
    NAKAGIRI T, INOUE M, MINAMI M, et al. Immunology mini-review: the basics of T(H)17 and interleukin-6 in transplantation[J]. Transplant Proc, 2012, 44(4): 1035- 1040. DOI: 10.1016/j.transproceed.2011.12.032.
    [23]
    秦建杰, 吕凌.白细胞介素17在器官移植排斥中的作用及机制[J].临床肝胆病杂志, 2012, 28(11): 812-814. http://med.wanfangdata.com.cn/Paper/Detail/PeriodicalPaper_lcgdbzz201211003

    QIN JJ, LYU L. The role and molecular mechanism of interleukin-17 in organ transplant rejection[J]. J Clin Hepatol, 2012, 28(11): 812-814. http://med.wanfangdata.com.cn/Paper/Detail/PeriodicalPaper_lcgdbzz201211003
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(3)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (93) PDF downloads(8) Cited by()
    Proportional views
    Related

    WeChat Subscription Account

    Wechat Service Account

    Contact Us
    • Tel：020-38736410
    • Email: organtranspl@163.com
    • Address：The Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou
    • Editorial Office of Organ Transplantation  粤ICP备2021030844号
    Links

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return