Xi LI, Dan-xu MA, Lei ZHANG, Ting ZHANG, Li WANG, Qun SHI, Qian WANG, Qing-jun WU, Xuan ZHANG, Feng-chun ZHANG, Yong-zhe LI. Expression of Perforin in the Peripheral Blood of Patients with Primary Biliary Cirrhosis and Its Clinical Significance[J]. Medical Journal of Peking Union Medical College Hospital, 2010, 1(2): 125-131.
Citation: Xi LI, Dan-xu MA, Lei ZHANG, Ting ZHANG, Li WANG, Qun SHI, Qian WANG, Qing-jun WU, Xuan ZHANG, Feng-chun ZHANG, Yong-zhe LI. Expression of Perforin in the Peripheral Blood of Patients with Primary Biliary Cirrhosis and Its Clinical Significance[J]. Medical Journal of Peking Union Medical College Hospital, 2010, 1(2): 125-131.

Expression of Perforin in the Peripheral Blood of Patients with Primary Biliary Cirrhosis and Its Clinical Significance

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  • Corresponding author:

    LI Yong-zhe Tel: 010-88068795, E-mail:yongzhelipumch@yahoo.com.cn

  • Received Date: July 29, 2010
  • Issue Publish Date: October 29, 2010
  •   Objective  To study the expression of perforin (also known as pore-forming protein, PFP) in the peripheral blood of patients with primary biliary cirrhosis (PBC) and to analyze the clinical significance of PFP in the pathogenesis of PBC.
      Methods  Peripheral blood mononuclear cells PFP mRNA were detected by real-time RT-PCR assay in 86 PBC patients, 56 chronic hepatitis B patients, and 69 health controls. The expressions of PFP protein in CD3-CD56+natural killer cells (NK), CD3+CD8+cytotoxic T lymphocytes (CTL), and CD3+CD56+natural killer T lymphocytes (NKT) were examined by tricolour flow cytometry.
      Results  The mRNA expression of PFP was significantly higher in PBC patients (P < 0.05). The percentage of lymphocyte subsets was not significantly different among the three groups (P>0.05), while the percentage of PFP in the three lymphocyte subsets in PBC patients was significantly higher than those in health controls (P < 0.01). The Mayo risk score was significantly correlated with the gene expression of PFP and the percentage of PFP in three types of cells in PBC patients (P < 0.05). The percentage of PFP in NK and CTL cells were also positively correlated with the levels of total bilirubin in PBC patients (P < 0.05).
      Conclusions  PFP shows abnormal expression in PBC patients, suggesting that PFP may be involved in the pathogenesis of PBC. The percentages of PFP-positive NK, CTL, and NKT cells can be used as effective indicators in predicting the survival of PBC patients.
  • [1]
    Lleo A, Selmi C, Invernizzi P, et al.Apotopes and the biliary specificity of primary biliary cirrhosis[J]. Hepatology, 2009, 49:871-879. DOI: 10.1002/hep.22736
    [2]
    Lleo A, Selmi C, Invernizzi P, et al.The consequences of apoptosis in autoimmunity[J]. J Autoimmun, 2008, 31: 257-262. DOI: 10.1016/j.jaut.2008.04.009
    [3]
    American Association for Study of Liver Diseases.Primary biliary cirrhosis[J]. Hepatology, 2009, 50:291-308. DOI: 10.1002/hep.22906
    [4]
    Bird PI, Trapani JA, Villadangos JA.Endolysosomal proteases and their inhibitors in immunity[J]. Nat Rev Immunol, 2009, 9:871-882. DOI: 10.1038/nri2671
    [5]
    Guy CS, Rankin SL, Wang J, et al.Hepatocytes can induce death of contacted cells via perforin-dependent mechanism[J]. Hepatology, 2008, 47:1691-1701. DOI: 10.1002/hep.22228
    [6]
    Potter S, Chan-Ling T, Ball HJ, et al.Perforinme diated apoptosis of cerebral microvascular endothelial cells during experimental cerebral malaria[J]. Int J Parasitol, 2006, 36:485-496. DOI: 10.1016/j.ijpara.2005.12.005
    [7]
    Waterhouse NJ, Sutton VR, Sedelies KA, et al.Cytotoxic T lymphocyte-induced killing in the absence of granzymes A and B is unique and distinct from both apoptosis and perforin-dependent lysis[J]. J Cell Biol, 2006, 173:133-144. DOI: 10.1083/jcb.200510072
    [8]
    Chuang YH, Lian ZX, Tsuneyama K, et al.Increased killing activity and decreased cytokine production in NK cells in patients with primary biliary cirrhosis[J]. J Autoimmun, 2006, 26:232-240. DOI: 10.1016/j.jaut.2006.04.001
    [9]
    Harada K, Ozaki S, Gershwin ME, et al.Enhanced apoptosis relates to bile duct loss in primary biliary cirrhosis[J]. Hepatology, 1997, 26:1399-1405. DOI: 10.1002/hep.510260604
    [10]
    Dong Z, Wei H, Sun R, et al.Involvement of natural killer cells in PolyI:C-induced liver injury[J]. J Hepatol, 2004, 41:966-973. DOI: 10.1016/j.jhep.2004.08.021
    [11]
    Ochi M, Ohdan H, Mitsuta H, et al.Liver NK cells expressing TRAIL are toxic against self hepatocytes in mice [J]. Hepatology, 2004, 39:1321-1331. DOI: 10.1002/hep.20204
    [12]
    Selmi C, Lleo A, Pasini S, et al.Innate immunity and primary biliary cirrhosis[J]. Curr Mol Med, 2009, 9:45-51. DOI: 10.2174/156652409787314525
    [13]
    Ahmed AF, Ohtani H, Nio M, et al.CD8 + T cells infiltrating into bile ducts inbiliary atresia do not appear to function as cytotoxic T cells:a clinicopathological analysis[J]. J Pathol, 2001, 193:383-389. DOI: 10.1002/1096-9896(2000)9999:9999<::AID-PATH793>3.0.CO;2-O
    [14]
    Harada K, Nakanuma Y.Molecular mechanisms of cholangiopathy in primary biliary cirrhosis[J]. Med Mol Morphol, 2006, 39:55-61. DOI: 10.1007/s00795-006-0321-z
    [15]
    Piccioli D, Sbrana S, Melandri E, et al.Contact-dependent stimulation and inhibition of dendritic cells by natural killer cells[J]. J Exp Med, 2002, 195:335-341. DOI: 10.1084/jem.20010934
    [16]
    Gerosa F, Gobbi A, Zorzi P, et al.The reciprocal interaction of NK cells with plasmacytoid or myeloid dendritic cells profoundly affects innate resistance functions[J]. J Immunol, 2005, 174:727-734. DOI: 10.4049/jimmunol.174.2.727
    [17]
    Johansson S, Hall H, Berg L, et al.NK cells inautoimmune disease[J]. Curr Top Microbiol Immunol, 2006, 298:259-277. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=10.1080/0891693042000196174
    [18]
    Padgett KA, Selmi C, Kenny TP, et al.Phylogenetic and immunological definition of four lipoylated proteins from Novosphingobium aromaticivorans, implications for primary biliary cirrhosis[J]. J Autoimmun, 2005, 24:209-219. DOI: 10.1016/j.jaut.2005.01.012
    [19]
    Mattner J, Savage PB, Leung P, et al.Liver autoimmunity triggered by microbial activation of natural killer T cells[J]. Cell Host Microbe, 2008, 3:304-315. DOI: 10.1016/j.chom.2008.03.009
    [20]
    Kita H, Naidenko OV, Kronenberg M, et al.Quantitation and phenotypic analysis of natural killer T cells in primary biliary cirrhosis using a human CD1 d tetramer[J]. Gastroenterology, 2002, 123:1031-1043. DOI: 10.1053/gast.2002.36020
    [21]
    Jones DE.Pathogenesis of primary biliary cirrhosis[J]. Gut, 2007, 56:1615-1624.
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