β2糖蛋白I与乙型肝炎表面抗原亲合力的研究
|
摘要
乙型肝炎病毒(HBV)是一种嗜肝脱氧核糖核酸病毒,目前全球约有4亿人群感染HBV。多年来学者对HBV感染肝细胞的早期过程进行研究,提出了多种观点并对可能的靶细胞受体进行鉴定,但仍无定论。β2糖蛋白I(β2-GPI)又称为载脂蛋白H,是血浆中一种含量较丰富的糖蛋白。近年研究认为,β2-GPI是抗磷脂抗体综合征(APS)的主要抗原之一。APS是与抗磷脂抗体(aPL)密切相关,是以血栓形成、习惯性流产和血小板减少等症状为特点的一组综合征。β2-GPI与aPL结合后能识别带负电荷的磷脂复合物,并使β2-GPI的表面结构发生变化,使机体易形成血栓。随着研究的拓展,Mehdi发现重组乙型肝炎表面抗原(rHBsAg)可与正常人肝细胞膜通过β2-GPI在膜外结合,表明β2-GPI可能参与HBV感染肝细胞。本研究组深入研究后提出,β2-GPI可能作为中介分子,与HBsAg形成复合物,再与肝细胞膜表面的特异性蛋白结合,从而介导HBV入肝过程。研究组已从肝癌细胞株SMMC-7721表面经鉴定出结合蛋白为膜联蛋白Ⅱ。在本研究中,我们将着重探讨β2-GPI与HBsAg特异性结合的亲和力及二者相互作用的机制,为上述观点提供更有力的实验依据,为今后的研究奠定基础。本研究利用大肠杆菌M15(pQE30-hβ2-GPI)高效表达目的蛋白,通过亲和层析纯化带有融合6个组氨酸标签的β2-GPI包涵体,并进行复性。原核系统表达的目的蛋白具有无糖基化修饰的特点,故这种rβ2-GPI可用于研究分子构象对蛋白结合作用的影响。我们首次利用放射性免疫法(radioimmunoassay,RIA)测定人β2GPI与rHBsAg结合的亲和常数(Ka),以此推断血浆中β2GPI与HBsAg的亲和力,并通过亲和常数比较与原核系统表达的rβ2-GPI免疫活性的差异。梯度浓度的两组来源不同的β2GPI分别与125I-rHBsAg结合,利用标准曲线Adrion法分别测得两组蛋白的Ka。采用嵌套实验设计进行数据分析,血浆中提取的β2-GPI组与原核系统表达的rβ2-GPI组的Ka无明显统计学差异(P>0.05)。最终求得血浆人β2-GPI组:Ka1=(2.795±1.846)×10~8 L/ mol。结果表明血浆β2-GPI与HBsAg结合的亲和力较强,且血浆中提取的β2-GPI与原核系统表达的rβ2-GPI与rHBsAg的结合力相似。我们得出结论,血浆中β2-GPI与HBsAg亲和力强,可能在血浆中二者较易形成复合物,且二者的结合与β2GPI的糖基化结构无关,即糖基化与否不影响β2-GPI的免疫活性。因此,β2-GPI无论发生何种构象改变,均不影响其与HBsAg的结合。这种结合可能参与介导HBV嗜肝过程,甚至参与肝细胞癌的发生发展。
Objective: Hepatitis B virus (HBV) infection is one of the most challenging global public health problems. Beta 2-Glycoprotein I (β2-GPI) is an enriched glycoprotein in plasma, which is a single-chain protein with 326 amino acids, containing four N-linked glycosylation sites.β2-GPI is one of the major autoantigen in the antiphospholipid antibody syndrome. A recent study showed thatβ2-GPI binding with HBsAg played a role in the process of HBV infection.So our research focused on the affinity betweenβ2-GPI and HBsAg and the influence of glycosylation ofβ2-GPI to the binding. This survey supplied the experimental evidences for HBV hepatotropic mechanism.
Methods: We studied the affinity ofβ2-GPI binding to rHBsAg. rHBsAg was radiolabeled with Na 125I by using chloramine-t, and the affinity constant (Ka) was checked by radioimmunoassay (RIA). The optimization of temperature and time of the binding ofβ2-GPI and 125I-rHBsAg were observed. The doubling dilution of 125I– rHBsAg bound to gradient concentration ofβ2-GPI from the plasma. Then, the precipitates were separated by the method of competitive conjugation, and their radio-counting checked was drawn on the double logarithmic paper. Ka1 was calculated by means of the Adrion. Also, we had expressed rβ2-GPI in E.coli M15 (pQE30-hβ2-GPI) which was non- glycosylated. They were purified through nickel chromatography and renaturated. By the same above-mentioned way, the Ka2 of rβ2-GPI binding to 125I– rHBsAg was measured.
Results: The specific activity of 125I-rHBsAg is (2.6-2.8)×106 Bq/μg. Following the binding curve, the best temperature and time is 37℃and 4 hours. The Ka1 of the group ofβ2-GPI binding to rHBsAg are (2.075±0.049)×10~8 L/mol、(2.25±0.099)×10~8 L/mol、(5.5±0.665)×10~8 L/mol、(1.355±0.064)×10~8 L/mol;The Ka2 of rβ2-GPI expressed by E.coil are(2.055±0.106)×108 L/mol、( 2.22±0.028)×10~8L/mol、(3.485±0.050)×10~8 L/mol、(4.245±0.134)×10~8 L/mol。According to the summary of β2-GPI from two separate sources binding to rHBsAg, there was no difference between Ka1 and Ka2 (P>0.05) by statistical analysis. Finally,the results of affinity constants of twoβ2-GPI groups were respectively (2.795±1.846)×10~8 L/ mol and (3.001±1.049)×10~8 L/ mol.
Conclusion:The affinity ofβ2-GPI and HBsAg are a strong bind in plasma (2.795±1.846)×10~8 L/ mol) and the glycosylation ofβ2-GPI has no effect on this conjugation.
Objective: Hepatitis B virus (HBV) infection is one of the most challenging global public health problems. Beta 2-Glycoprotein I (β2-GPI) is an enriched glycoprotein in plasma, which is a single-chain protein with 326 amino acids, containing four N-linked glycosylation sites.β2-GPI is one of the major autoantigen in the antiphospholipid antibody syndrome. A recent study showed thatβ2-GPI binding with HBsAg played a role in the process of HBV infection.So our research focused on the affinity betweenβ2-GPI and HBsAg and the influence of glycosylation ofβ2-GPI to the binding. This survey supplied the experimental evidences for HBV hepatotropic mechanism.
Methods: We studied the affinity ofβ2-GPI binding to rHBsAg. rHBsAg was radiolabeled with Na 125I by using chloramine-t, and the affinity constant (Ka) was checked by radioimmunoassay (RIA). The optimization of temperature and time of the binding ofβ2-GPI and 125I-rHBsAg were observed. The doubling dilution of 125I– rHBsAg bound to gradient concentration ofβ2-GPI from the plasma. Then, the precipitates were separated by the method of competitive conjugation, and their radio-counting checked was drawn on the double logarithmic paper. Ka1 was calculated by means of the Adrion. Also, we had expressed rβ2-GPI in E.coli M15 (pQE30-hβ2-GPI) which was non- glycosylated. They were purified through nickel chromatography and renaturated. By the same above-mentioned way, the Ka2 of rβ2-GPI binding to 125I– rHBsAg was measured.
Results: The specific activity of 125I-rHBsAg is (2.6-2.8)×106 Bq/μg. Following the binding curve, the best temperature and time is 37℃and 4 hours. The Ka1 of the group ofβ2-GPI binding to rHBsAg are (2.075±0.049)×10~8 L/mol、(2.25±0.099)×10~8 L/mol、(5.5±0.665)×10~8 L/mol、(1.355±0.064)×10~8 L/mol;The Ka2 of rβ2-GPI expressed by E.coil are(2.055±0.106)×108 L/mol、( 2.22±0.028)×10~8L/mol、(3.485±0.050)×10~8 L/mol、(4.245±0.134)×10~8 L/mol。According to the summary of β2-GPI from two separate sources binding to rHBsAg, there was no difference between Ka1 and Ka2 (P>0.05) by statistical analysis. Finally,the results of affinity constants of twoβ2-GPI groups were respectively (2.795±1.846)×10~8 L/ mol and (3.001±1.049)×10~8 L/ mol.
Conclusion:The affinity ofβ2-GPI and HBsAg are a strong bind in plasma (2.795±1.846)×10~8 L/ mol) and the glycosylation ofβ2-GPI has no effect on this conjugation.
引文
[1] Steinkasserer A, Estaller C, Weiss EH, et al. Complete nucleotide and deduced amino acid sequence of humanβ2-glycoprotein I [J]. Biochem J, 1991, 277:387-91.
[2] Matsuura E, Igarashi Y, Fujimoto M, et al. Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease [J]. Lancet, 1990, 336(8708):177-8.
[3] Roubey RA, Eisenberg RA, Harper MF, et al. "Anticardiolipin" autoantibodies recognize beta 2-glycoprotein I in the absence of phospholipid. Importance of Ag density and bivalent binding [J]. J Immunol. 1995 Jan 15;154(2):954-60.
[4] Mehdi H, Kaplan MJ, Anlar FY, et al. Hepatitis B virus surface antigen binds to apolipoprotein H [J]. J Virology, 1994, Apr: 2415-24.
[5] Schulze A, Gripon P, Urban S. Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans [J]. Hepatology, 2007 Dec,46(6): 1759- 68.
[6] Pontisso P, Petit MA, Bankowski MJ, et al. Human liver plasma membranes contain receptors for the hepatitis B virus pre-S1 region and, via polymerized human serum albumin, for the pre-S2 region [J]. J Virol,1989 May,63(5):1981-8.
[7] Mehdi H, Yang X, Peeples ME. An altered form of apolipoprotein H binds hepatitis B virus surface antigen most efficiently [J]. Virology.1996 Mar 1;217(1):58-66.
[8] Stefas I, Rucheton M,D'Angeac AD, et al. Hepatitis B virus dane particles bind to human plasma apolipoprotein H [J]. Hepatology, 2001,33(1): 207-17.
[9]高沿航,高普均,王丹,等.β2糖蛋白I与乙型肝炎病毒嗜肝性的关系[J].中华肝脏病杂志,2006,14(8):569-71。
[10]高沿航,高普均,王丹,等。SMMC 7721肝癌细胞膜上β2糖蛋白I受体表达[J],世界华人杂志,2006,14(17):1731-4。
[11] ShiY, Liu YW,Gao PJ,et al. Identification of theβ2GP I binding receptor on hepatocyte membrane [J],Zhonghua Yixue Zazhi,2007,87(34):2429-31。
[12] Mehdi, H., M. Nunn, D. M. Steel, et al. Nucleotide sequence and expression of the human gene encoding apolipoprotein H (β2-glycoprotein I) [J]. Gene, 1991, 108:293-8.
[13] Gabius H,Andre S,Kalmer H ET al.The sugar code: functional lectinomics [J].Biochim Biophys Acta. 2002 Sep 19; 1572(2-3):165-77.
[14] Ioannou Y, Giles I, Lambrianides A,et al. A novel expression system of domain I of humanbeta2 glycoprotein I in Escherichia coli [J]. BMC Biotechnol, 2006 Feb, 10; 6:8.
[15] Yiannis Ioannou, Charis Pericleous, Ian Giles, et al. Binding of Antiphospholipid Antibodies to Discontinuous Epitopes on Domain I of Humanβ2-Glycoprotein I [J]. ARTHRITIS & RHEUMATISM, January 2007, 56, 1, 280–290.
[16] Schultze HE, Hiede K, Haupt H. Uber ein bisher unbekanntes niederm- olekularesβ2-Globulin des Humanserums [J]. Naturwissenscha- ften.1961; 48: 719.
[17] Wang HH, Chiang AN. Cloning and characterization of the human beta2- glycoprotein I (beta2-GPI) gene promoter: roles of the atypical TATA box and hepatic nuclear factor-1 alpha in regulating beta2-GPI promoter activity [J]. Biochem J, 2004, 380:455-63.
[18] Sheng Y, Sali A, Herzog H, et al. Site directed mutagenesis of recombinant humanβ2-glycoprotein I identifies a cluster of lysine residues that are critical for phospholipid binding and anti-cardiolipin antibody activity [J]. J Immunol 1996, 157:3744-51.
[19] Alarcon-segovia D. Climical manifestations of the antiphospholipid syndrome [J]. J Rheumatol, 1992, 19:1778-81.
[20] Guerin J, Sheng Y, Reddel S, et al. Heparin inhibits the binding of beta 2-glycoprotein I to phospholipids and promotes the plasmin-mediated inactivationof this blood protein. Elucidation of the consequences of the two biological events in patients with the antiphospholipid syndrome [J]. J Biol Chem, 2002, 277:2644-9.
[21] Wilson WA, Gharavi AE. Genetic risk factors for aPL syndrome [J]. Lupus,1996,5:398-403.
[22] Hammel M, Schwar to bacher R, Gries A, et al. Mechanism of the interaction of beta 2-glycoprotein 1 with negatirely charged phospholipid membranes [J]. Biochemistry, 2001, 40(47):14173-81.
[23] Nimpf J, Bevers EM, Bomans PH, et al. Prothrombinase activity of human platelets is inhibited byβ2-glycoprotein-I [J]. Biochim Biophys Acta, 1986, 884(1):142-9.
[24] Schousboe I, Rasmussen MS. Synchronized inhibition of the phospholipid mediated autoactivation of factor XII in plasma byβ2-glycoprotein I and anti-β2-glycoprotein I [J]. Thromb Haemost, 1995, 73(5):798-804.
[25] Nimpf J, Wurm H, Kostner GM.Beta 2-glycoprotein-I (apo-H) inhibits the release reaction of human platelets during ADP-induced aggregation [J]. Atherosclerosis, 1987 Feb, 63(2-3):109-14.
[26] Shi T, Iverson GM, Qi JC, et al.β2-glycoprotein I binds factor XI and inhibits its activation by thrombin and factor XIIa: loss of inhibition by clipped beta 2-glycoprotein I [J]. Proc Natl Acad Sci U S A, 2004, 101(11):3939-44.
[27] López-Lira F, Rosales-León L, Martínez VM,et al.The role of beta2-glycoprotein I (beta2GPI) in the activation of plasminogen [J]. Biochim Biophys Acta, 2006 Apr, 1764(4):815-23.
[28] Mori T, Takeya H, Nishioka J,et al.β2-Glycoprotein I modulates the anticoagulant activity of activated protein C on the phospholipid surface [J]. Thromb Haemost, 1996, 75(1):49-55.
[29] Sheng Y, Reddel SW, Herzog H, et al. Impaired thrombin generation inβ2-glycoprotein I null mice [J]. J Biol Chem, 2001, 276(17): 13817-21.
[30] Lokar M, Urbanija J, Frank M,et al.Agglutination of like-charged red blood cells induced by binding of beta(2)-glycoprotein I to outer cell surface [J]. Bioelectrochemistry,2008 Aug,73(2):110-6.
[31] Haginara Y, Hong DP, Hoshino M, et al. Aggregation of beta2- glycoprotein I induced by sodium lauryl suffate and lysophos pholipids [J].Buicgenstrt,2002 Jan,341(3):1020-6.
[32] Krilis SA, Sheng YH, Kandiah DA. The role of beta 2-glycoprotein I in the antiphospholipid syndrome [J]. Lupus, 1996 Apr, 5(2):150-2.
[33] Yan X, Morselt HW, Scherphof GL,et al.The role of beta2- glycoprotein I in liposome-hepatocyte interaction [J]. Biochim Biophys Acta, 2004 Dec 15, 1667 (2):208-14.
[34] Matsuura E, Kobayashi K, Inoue K,et al. Oxidized LDL/beta2- glycoprotein I complexes: new aspects in atherosclerosis [J]. Lupus, 2005, 14(9):736-41.
[35] Matsuura E, Kobayashi K, Tabuchi M, Lopez LR. Oxidative modification of low-density lipoprotein and immune regulation of atherosclerosis[J]. Prog Lipid Re, 2006, 45:466-86.
[36] Matsuura E, Hughes GR, Khamashta MA. Oxidation of LDL and its clinical implication [J]. Autoimmun Rev, 2008 Jul,7(7): 558-66.
[37] Verhoven B, Schlegel RA,Williamson P. Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic T lymphocytes [J]. Journal of Experimental Medicine, 1995, 182: 1597–1601.
[38] Savill J, Dransfield I, Gregory C, et al. A blast from the past: Clearance of apoptotic cells regulates immune responses [J].Nature Reviews Immunology, 2002, 2(12):965-75.
[39] Balasubramanian K, Maiti SN, Schroit AJ. Recruitment of beta-2 glycoprotein 1 to cell surfaces in extrinsic and intrinsic apoptosis [J]. Apoptosis, 2005 Mar,10(2):439-46.
[40] Maiti SN, Balasubramanian K, Ramoth JA, et al. Beta-2 glycoprotein I-dependent macrophage uptake of apoptotic cells. Binding to lipoprotein receptor-related protein receptor family members [J]. J Biol Chem, 2008 Feb 15,283(7):3761-6.
[41] Chonn A, Semple SC, Cullis PR.Beta 2 glycoprotein I is a major protein associated with very rapidly cleared liposomes in vivo, suggesting a significant role in the immune clearance of "non-self" particles [J]. J Biol Chem, 1995 Oct 27,270(43):25845-9.
[42] Hasunuma Y, Matsuura E, Makita Z, et al. Involvement ofβ2- glycoprotein I and anticardiolipin antibodies in oxidatively modified low-density lipoprotein uptake by macrophages [J]. Clin Exp Immunol, 1997, 107:569-73.
[43] Neurath AR, Strick N.The putative cell receptors for hepatitis B virus (HBV), annexin V, and apolipoprotein H, bind to lipid components of HBV [J]. Virology,1994 Oct,204(1):475-7.
[44] Zachou K, Liaskos C, Christodoulou DK,et al.Anti-cardiolipin antibodies in patients with chronic viral hepatitis are independent of beta2- glycoprotein I cofactor or features of antiphospholipid syndrome [J]. Eur J Clin Invest, 2003 Feb, 33(2):161-8.
[45]高普均,朴云峰,王小丛,等.抗β2糖蛋白I抗体与乙型肝炎后肝硬化细胞外基质的相关性研究[J].中国实用内科杂志,2002 , 22 : 732-4。
[46] Martinuc Porobic J , Avcin T , Bozic B , et al . Anti-phospholipid antibodies following vaccination with recombinant hepatitis B vaccine [J]. Clin Exp Immunol, 2005, 142: 377-80.
[47] Yuste JR, Prieto J.Anticardiolipin antibodies in chronic viral hepatitis. Do they have clinical consequences [J]? Eur J Gastroenterol Hepatol, 2003, 15(7):717-9.
[48] Elefsiniotis IS, Diamantis ID, Dourakis SP,et al. Anticardiolipin antibodies in chronic hepatitis B and chronic hepatitis D infection, and hepatitis B-related hepatocellular carcinoma. Relationship with portal vein thrombosis [J]. Eur J Gastroenterol Hepatol, 2003 Jul, 15(7):721-6.
[49] Song KS , Kim HK. Prevalence of beta2-glycoprotein I antibody in patient s wit h liver cirrhosis: relationship wit h beta2-glycoprotein I plasma levels and t hrombosis [J]. Clin Appl Thromb Hemost, 2004, 10: 183-6.
[50] Habibagahi Z,Nazarinia MA,Aflaki E,et al.Anticardiolipin and anti-beta2- glycoproteinI antibodies in patients with hepatitis B and C infections [J]. Iran J Immunol,2007 Sep,4(3):161-6.
[51] Schwarzenbacher R , Zeth K, Diederichs K, et al. Crystal structure of humanβ2-glycoprotein I:implications for phospholipid binding and the antiphospholipid syndrome [J]. EMBO J, 1999, 18: 6228 -39.
[52] Von Landenberg P, Baumgartner M, Schoelmerich J, et al. Clinical relevance ofantiphospholipid antibodies in primary biliary cirrhosis [J]. Ann N Y Acad Sci, 2005, 1051: 20-8.
[53] Gabeta S, Norman GL, Gatselis N, et al. IgA Anti-β2GPI Antibodies in Patients with Autoimmune Liver Diseases [J]. J Clin Immunol,2008 Jun 13, 57-62.
[54] Chedid A, Chadalawada KR,Morgan TR,et al. Phospholipid antibodies in alcoholic liver disease [J]. Hepatology,1994 , 20 : 1465-71。
[55] Rolla R , Vay D , Mot taran E , et al . Antiphospholipid antibodies associated with alcoholic liver disease specifically recognize oxidised phospholipids [J]. Gut, 2001, 49: 852-9.
[56] Perney P, Biron-Andréani C, Joomaye Z, et al.Antiphospholipid antibodies in alcoholic liver disease are influenced by histological damage but not by alcohol consumption [J]. Lupus, 2000, 9(6):451-5.
[57] Vay D, Rigamonti C, Vidali M, et al. Anti-phospholipid antibodies associated with alcoholic liver disease target oxidized phosphatidylserine on apoptotic cell plasma membranes [J]. J Hepatol,2006 Jan,44(1):183-9.
[58] Natori S, Rust C, Stadheim LM, et al. Hepatocyte apoptosis is a pathological feature of human alcoholic hepatitis [J]. J Hepatol,2001,34:248-53.
[59] Neurath AR, Seto B, Strick N. Antibodies to synthetic peptides from the preS1 region of the hepatitis B virus (HBV) envelope (env) protein are virus-neutralizing and protective [J]. Vaccine,1989 Jun,7(3):234- 6.
[60] Glebe D, Urban S, Knoop EV, et al. Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and tupaia hepatocytes [J]. Gastroenterology, 2005 Jul, 129 (1):234-45.
[61] Engelke M, Mills K, Seitz S, et al. Characterization of a hepatitis B and hepatitis delta virus receptor binding site [J]. Hepatology, 2006 Apr, 43(4):750-60.
[62] Gripon P, Cannie I, Urban S. Efficient inhibition of hepatitis B virus infection by acylated peptides derived from the large viral surface protein [J]. J Virol,2005 Feb,79(3):1613-22.
[63] Barrera A, Guerra B,Notvall L, et al. mapping of the hepatitis B virus pre-S1 domain involved in receptor recognition [J]. J Virol, 2005 Aug,79 (15): 9786-98.
[64] Stoeckl, L., A. Funk, Kopitzki A,et al. Identification of a structural motif crucial for infectivity of hepatitis B viruses [J]. Proc. Natl. Acad. Sci. USA, 2006, Apr 25; 103(17): 6730-4.
[65] Gudima S, Meier A, Dunbrack R, et al. Two potentially important elements of thehepatitis B virus large envelope protein are dispensable for the infectivity of hepatitis delta virus [J]. J Virol, 2007, 81(8): 4343-7.
[66] Blanchet M, Sureau C. Infectivity determinants of the hepatitis B virus pre-S domain are confined to the N-terminal 75 amino acid residues [J]. J Virol, 2007 Jun, 81(11):5841-9.
[67] Guibinga GH, Miyanohara A, Esko JD, et al. Cell surface heparan sulfate is a receptor for attachment of envelope protein-free retrovirus-like particles and VSV-G pseudotyped MLV-derived retrovirus vectors to target cells [J]. Mol Ther, 2002 May,5(5 Pt 1):538-46.
[68] Schulze A, Gripon P, Urban S. Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans [J]. Hepatology, 2007 Dec,46(6): 1759- 68.
[69] Leistner CM, Gruen-Bernhard S, Glebe D. Role of glycosaminoglycans for binding and infection of hepatitis B virus [J]. Cell Microbiol, 2008 Jan, 10(1): 122-33.
[70] Diao J, Slaney DM, Michalak TI. Modulation of the outcome and severity of hepadnaviral hepatitis in woodchucks by antibodies to hepatic asialoglycoprotein receptor [J]. Hepatology, 2003 Sep, 38(3):629-38.
[71] Owada T, Matsubayashi K, Sakata H. et al. Interaction between desialylated hepatitis B virus and asialoglycoprotein receptor on hepatocytes may be indispensable for viral binding and entry [J]. J Viral Hepat. 2006 Jan,13(1):11-8.
[72] Wisse E, Braet F, Luo D, et al. Structure and function of sinusoidal lining cells in the liver [J]. Toxicol Pathol, 1996, 24(1):100-11.
[73] De Falco S, Ruvoletto MG, Verdoliva A, et al. Cloning and expression of a novel hepatitis B virus-binding protein from HepG2 cells [J] . J Biol Chem, 2001 Sep 28,276(39): 36613-23.
[74] Xia HB, Chen ZY, Chen XG. Overexpression of hepatitis B virus-binding protein, squamous cell carcinoma antigen 1, extends retention of hepatitis B virus in mouse liver [J]. Acta Biochim Biophys Sin (Shanghai), 2006 Jul, 38(7):484-91.
[75] Pontisso P, Calabrese F, Benvegnu L et al. Over expression of squamous cell carcinoma antigen variants in hepatocellular carcinoma [J]. Br J Cancer,2004 Feb 23,90 (4):833-7.
[76] Beneduce L, Castaldi F, Marino M et al. Squamous cell carcinoma antigen- immunoglobulin M complexes as novel biomarkers for hepatocellular carcinoma [J]. Cancer, 2005 Jun 15,103 (12): 2558-65.
[77] Urban S. Binding of duck carboxypeptidase D to duck hepatitis B virus [J]. Methods Mol Med, 2004, 95: 199-212.
[78] Maenz C, Chang SF, Iwanski A, et al. Entry of duck hepatitis B virus into primary duckliver and kidney cells after discovery of a fusogenic region within the large surface protein [J]. J Virol, 2007 May, 81(10):5014-23.
[79] Deng Q, Zhai JW, Michel ML, et al. Identification and characterization of peptides that interact with hepatitis B virus via the putative receptor binding site [J]. J Virol, 2007 Apr, 81(8): 4244-54.
[80] Gripon P, Rumin S, Urban S, et al. Infection of a human hepatoma cell line by hepatitis B virus [J]. Proc Natl Acad Sci U S A, 2002, 99:15655-60.
[81] Glebe D, Aliakbari M, Krass P, et al. Pre-S1 antigen-dependent infection of Tupaia hepatocyte cultures with human hepatitis B virus [J]. J Virol, 2003 Sep, 77(17):9511-21.
[82] de Laat B, Derksen RH, van Lummel M,et al. Pathogenic anti-beta2-glycoprotein I antibodies recognize domain I of beta2-glycoprotein I only after a conformational change.Blood,2006, Mar 1;107(5):1916-24.
[83] Igarashi M, Matsuura E. Human beta2-glycoprotein I as an anticardiolipin cofactor determined using mutants expressed by a baculovirus system [J]. Blood, 1996 Apr 15, 87(8):3262-70.
[84] Mehdi H, Naqvi A, Kamboh MI. Recombinant hepatitis B surface antigen and anionic phospholipids share a binding region in the fifth domain of beta2-glycoprotein I (apolipoprotein H)[J]. Biochim Biophys Acta. 2008 Mar;1782(3):163-8.
[85] Alarcon-segovia D. Climical manifestations of the antiphospholipid syndrome [J]. J Rheumatol, 1992, 19:1778-81.
[86] Wang HH, Chiang AN. Cloning and characterization of the human beta2- glycoprotein I (beta2-GPI) gene promoter: roles of the atypical TATA box and hepatic nuclear factor-1 alpha in regulating beta2-GPI promoter activity [J]. Biochem J, 2004, 380:455-63.
[2] Matsuura E, Igarashi Y, Fujimoto M, et al. Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease [J]. Lancet, 1990, 336(8708):177-8.
[3] Roubey RA, Eisenberg RA, Harper MF, et al. "Anticardiolipin" autoantibodies recognize beta 2-glycoprotein I in the absence of phospholipid. Importance of Ag density and bivalent binding [J]. J Immunol. 1995 Jan 15;154(2):954-60.
[4] Mehdi H, Kaplan MJ, Anlar FY, et al. Hepatitis B virus surface antigen binds to apolipoprotein H [J]. J Virology, 1994, Apr: 2415-24.
[5] Schulze A, Gripon P, Urban S. Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans [J]. Hepatology, 2007 Dec,46(6): 1759- 68.
[6] Pontisso P, Petit MA, Bankowski MJ, et al. Human liver plasma membranes contain receptors for the hepatitis B virus pre-S1 region and, via polymerized human serum albumin, for the pre-S2 region [J]. J Virol,1989 May,63(5):1981-8.
[7] Mehdi H, Yang X, Peeples ME. An altered form of apolipoprotein H binds hepatitis B virus surface antigen most efficiently [J]. Virology.1996 Mar 1;217(1):58-66.
[8] Stefas I, Rucheton M,D'Angeac AD, et al. Hepatitis B virus dane particles bind to human plasma apolipoprotein H [J]. Hepatology, 2001,33(1): 207-17.
[9]高沿航,高普均,王丹,等.β2糖蛋白I与乙型肝炎病毒嗜肝性的关系[J].中华肝脏病杂志,2006,14(8):569-71。
[10]高沿航,高普均,王丹,等。SMMC 7721肝癌细胞膜上β2糖蛋白I受体表达[J],世界华人杂志,2006,14(17):1731-4。
[11] ShiY, Liu YW,Gao PJ,et al. Identification of theβ2GP I binding receptor on hepatocyte membrane [J],Zhonghua Yixue Zazhi,2007,87(34):2429-31。
[12] Mehdi, H., M. Nunn, D. M. Steel, et al. Nucleotide sequence and expression of the human gene encoding apolipoprotein H (β2-glycoprotein I) [J]. Gene, 1991, 108:293-8.
[13] Gabius H,Andre S,Kalmer H ET al.The sugar code: functional lectinomics [J].Biochim Biophys Acta. 2002 Sep 19; 1572(2-3):165-77.
[14] Ioannou Y, Giles I, Lambrianides A,et al. A novel expression system of domain I of humanbeta2 glycoprotein I in Escherichia coli [J]. BMC Biotechnol, 2006 Feb, 10; 6:8.
[15] Yiannis Ioannou, Charis Pericleous, Ian Giles, et al. Binding of Antiphospholipid Antibodies to Discontinuous Epitopes on Domain I of Humanβ2-Glycoprotein I [J]. ARTHRITIS & RHEUMATISM, January 2007, 56, 1, 280–290.
[16] Schultze HE, Hiede K, Haupt H. Uber ein bisher unbekanntes niederm- olekularesβ2-Globulin des Humanserums [J]. Naturwissenscha- ften.1961; 48: 719.
[17] Wang HH, Chiang AN. Cloning and characterization of the human beta2- glycoprotein I (beta2-GPI) gene promoter: roles of the atypical TATA box and hepatic nuclear factor-1 alpha in regulating beta2-GPI promoter activity [J]. Biochem J, 2004, 380:455-63.
[18] Sheng Y, Sali A, Herzog H, et al. Site directed mutagenesis of recombinant humanβ2-glycoprotein I identifies a cluster of lysine residues that are critical for phospholipid binding and anti-cardiolipin antibody activity [J]. J Immunol 1996, 157:3744-51.
[19] Alarcon-segovia D. Climical manifestations of the antiphospholipid syndrome [J]. J Rheumatol, 1992, 19:1778-81.
[20] Guerin J, Sheng Y, Reddel S, et al. Heparin inhibits the binding of beta 2-glycoprotein I to phospholipids and promotes the plasmin-mediated inactivationof this blood protein. Elucidation of the consequences of the two biological events in patients with the antiphospholipid syndrome [J]. J Biol Chem, 2002, 277:2644-9.
[21] Wilson WA, Gharavi AE. Genetic risk factors for aPL syndrome [J]. Lupus,1996,5:398-403.
[22] Hammel M, Schwar to bacher R, Gries A, et al. Mechanism of the interaction of beta 2-glycoprotein 1 with negatirely charged phospholipid membranes [J]. Biochemistry, 2001, 40(47):14173-81.
[23] Nimpf J, Bevers EM, Bomans PH, et al. Prothrombinase activity of human platelets is inhibited byβ2-glycoprotein-I [J]. Biochim Biophys Acta, 1986, 884(1):142-9.
[24] Schousboe I, Rasmussen MS. Synchronized inhibition of the phospholipid mediated autoactivation of factor XII in plasma byβ2-glycoprotein I and anti-β2-glycoprotein I [J]. Thromb Haemost, 1995, 73(5):798-804.
[25] Nimpf J, Wurm H, Kostner GM.Beta 2-glycoprotein-I (apo-H) inhibits the release reaction of human platelets during ADP-induced aggregation [J]. Atherosclerosis, 1987 Feb, 63(2-3):109-14.
[26] Shi T, Iverson GM, Qi JC, et al.β2-glycoprotein I binds factor XI and inhibits its activation by thrombin and factor XIIa: loss of inhibition by clipped beta 2-glycoprotein I [J]. Proc Natl Acad Sci U S A, 2004, 101(11):3939-44.
[27] López-Lira F, Rosales-León L, Martínez VM,et al.The role of beta2-glycoprotein I (beta2GPI) in the activation of plasminogen [J]. Biochim Biophys Acta, 2006 Apr, 1764(4):815-23.
[28] Mori T, Takeya H, Nishioka J,et al.β2-Glycoprotein I modulates the anticoagulant activity of activated protein C on the phospholipid surface [J]. Thromb Haemost, 1996, 75(1):49-55.
[29] Sheng Y, Reddel SW, Herzog H, et al. Impaired thrombin generation inβ2-glycoprotein I null mice [J]. J Biol Chem, 2001, 276(17): 13817-21.
[30] Lokar M, Urbanija J, Frank M,et al.Agglutination of like-charged red blood cells induced by binding of beta(2)-glycoprotein I to outer cell surface [J]. Bioelectrochemistry,2008 Aug,73(2):110-6.
[31] Haginara Y, Hong DP, Hoshino M, et al. Aggregation of beta2- glycoprotein I induced by sodium lauryl suffate and lysophos pholipids [J].Buicgenstrt,2002 Jan,341(3):1020-6.
[32] Krilis SA, Sheng YH, Kandiah DA. The role of beta 2-glycoprotein I in the antiphospholipid syndrome [J]. Lupus, 1996 Apr, 5(2):150-2.
[33] Yan X, Morselt HW, Scherphof GL,et al.The role of beta2- glycoprotein I in liposome-hepatocyte interaction [J]. Biochim Biophys Acta, 2004 Dec 15, 1667 (2):208-14.
[34] Matsuura E, Kobayashi K, Inoue K,et al. Oxidized LDL/beta2- glycoprotein I complexes: new aspects in atherosclerosis [J]. Lupus, 2005, 14(9):736-41.
[35] Matsuura E, Kobayashi K, Tabuchi M, Lopez LR. Oxidative modification of low-density lipoprotein and immune regulation of atherosclerosis[J]. Prog Lipid Re, 2006, 45:466-86.
[36] Matsuura E, Hughes GR, Khamashta MA. Oxidation of LDL and its clinical implication [J]. Autoimmun Rev, 2008 Jul,7(7): 558-66.
[37] Verhoven B, Schlegel RA,Williamson P. Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic T lymphocytes [J]. Journal of Experimental Medicine, 1995, 182: 1597–1601.
[38] Savill J, Dransfield I, Gregory C, et al. A blast from the past: Clearance of apoptotic cells regulates immune responses [J].Nature Reviews Immunology, 2002, 2(12):965-75.
[39] Balasubramanian K, Maiti SN, Schroit AJ. Recruitment of beta-2 glycoprotein 1 to cell surfaces in extrinsic and intrinsic apoptosis [J]. Apoptosis, 2005 Mar,10(2):439-46.
[40] Maiti SN, Balasubramanian K, Ramoth JA, et al. Beta-2 glycoprotein I-dependent macrophage uptake of apoptotic cells. Binding to lipoprotein receptor-related protein receptor family members [J]. J Biol Chem, 2008 Feb 15,283(7):3761-6.
[41] Chonn A, Semple SC, Cullis PR.Beta 2 glycoprotein I is a major protein associated with very rapidly cleared liposomes in vivo, suggesting a significant role in the immune clearance of "non-self" particles [J]. J Biol Chem, 1995 Oct 27,270(43):25845-9.
[42] Hasunuma Y, Matsuura E, Makita Z, et al. Involvement ofβ2- glycoprotein I and anticardiolipin antibodies in oxidatively modified low-density lipoprotein uptake by macrophages [J]. Clin Exp Immunol, 1997, 107:569-73.
[43] Neurath AR, Strick N.The putative cell receptors for hepatitis B virus (HBV), annexin V, and apolipoprotein H, bind to lipid components of HBV [J]. Virology,1994 Oct,204(1):475-7.
[44] Zachou K, Liaskos C, Christodoulou DK,et al.Anti-cardiolipin antibodies in patients with chronic viral hepatitis are independent of beta2- glycoprotein I cofactor or features of antiphospholipid syndrome [J]. Eur J Clin Invest, 2003 Feb, 33(2):161-8.
[45]高普均,朴云峰,王小丛,等.抗β2糖蛋白I抗体与乙型肝炎后肝硬化细胞外基质的相关性研究[J].中国实用内科杂志,2002 , 22 : 732-4。
[46] Martinuc Porobic J , Avcin T , Bozic B , et al . Anti-phospholipid antibodies following vaccination with recombinant hepatitis B vaccine [J]. Clin Exp Immunol, 2005, 142: 377-80.
[47] Yuste JR, Prieto J.Anticardiolipin antibodies in chronic viral hepatitis. Do they have clinical consequences [J]? Eur J Gastroenterol Hepatol, 2003, 15(7):717-9.
[48] Elefsiniotis IS, Diamantis ID, Dourakis SP,et al. Anticardiolipin antibodies in chronic hepatitis B and chronic hepatitis D infection, and hepatitis B-related hepatocellular carcinoma. Relationship with portal vein thrombosis [J]. Eur J Gastroenterol Hepatol, 2003 Jul, 15(7):721-6.
[49] Song KS , Kim HK. Prevalence of beta2-glycoprotein I antibody in patient s wit h liver cirrhosis: relationship wit h beta2-glycoprotein I plasma levels and t hrombosis [J]. Clin Appl Thromb Hemost, 2004, 10: 183-6.
[50] Habibagahi Z,Nazarinia MA,Aflaki E,et al.Anticardiolipin and anti-beta2- glycoproteinI antibodies in patients with hepatitis B and C infections [J]. Iran J Immunol,2007 Sep,4(3):161-6.
[51] Schwarzenbacher R , Zeth K, Diederichs K, et al. Crystal structure of humanβ2-glycoprotein I:implications for phospholipid binding and the antiphospholipid syndrome [J]. EMBO J, 1999, 18: 6228 -39.
[52] Von Landenberg P, Baumgartner M, Schoelmerich J, et al. Clinical relevance ofantiphospholipid antibodies in primary biliary cirrhosis [J]. Ann N Y Acad Sci, 2005, 1051: 20-8.
[53] Gabeta S, Norman GL, Gatselis N, et al. IgA Anti-β2GPI Antibodies in Patients with Autoimmune Liver Diseases [J]. J Clin Immunol,2008 Jun 13, 57-62.
[54] Chedid A, Chadalawada KR,Morgan TR,et al. Phospholipid antibodies in alcoholic liver disease [J]. Hepatology,1994 , 20 : 1465-71。
[55] Rolla R , Vay D , Mot taran E , et al . Antiphospholipid antibodies associated with alcoholic liver disease specifically recognize oxidised phospholipids [J]. Gut, 2001, 49: 852-9.
[56] Perney P, Biron-Andréani C, Joomaye Z, et al.Antiphospholipid antibodies in alcoholic liver disease are influenced by histological damage but not by alcohol consumption [J]. Lupus, 2000, 9(6):451-5.
[57] Vay D, Rigamonti C, Vidali M, et al. Anti-phospholipid antibodies associated with alcoholic liver disease target oxidized phosphatidylserine on apoptotic cell plasma membranes [J]. J Hepatol,2006 Jan,44(1):183-9.
[58] Natori S, Rust C, Stadheim LM, et al. Hepatocyte apoptosis is a pathological feature of human alcoholic hepatitis [J]. J Hepatol,2001,34:248-53.
[59] Neurath AR, Seto B, Strick N. Antibodies to synthetic peptides from the preS1 region of the hepatitis B virus (HBV) envelope (env) protein are virus-neutralizing and protective [J]. Vaccine,1989 Jun,7(3):234- 6.
[60] Glebe D, Urban S, Knoop EV, et al. Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and tupaia hepatocytes [J]. Gastroenterology, 2005 Jul, 129 (1):234-45.
[61] Engelke M, Mills K, Seitz S, et al. Characterization of a hepatitis B and hepatitis delta virus receptor binding site [J]. Hepatology, 2006 Apr, 43(4):750-60.
[62] Gripon P, Cannie I, Urban S. Efficient inhibition of hepatitis B virus infection by acylated peptides derived from the large viral surface protein [J]. J Virol,2005 Feb,79(3):1613-22.
[63] Barrera A, Guerra B,Notvall L, et al. mapping of the hepatitis B virus pre-S1 domain involved in receptor recognition [J]. J Virol, 2005 Aug,79 (15): 9786-98.
[64] Stoeckl, L., A. Funk, Kopitzki A,et al. Identification of a structural motif crucial for infectivity of hepatitis B viruses [J]. Proc. Natl. Acad. Sci. USA, 2006, Apr 25; 103(17): 6730-4.
[65] Gudima S, Meier A, Dunbrack R, et al. Two potentially important elements of thehepatitis B virus large envelope protein are dispensable for the infectivity of hepatitis delta virus [J]. J Virol, 2007, 81(8): 4343-7.
[66] Blanchet M, Sureau C. Infectivity determinants of the hepatitis B virus pre-S domain are confined to the N-terminal 75 amino acid residues [J]. J Virol, 2007 Jun, 81(11):5841-9.
[67] Guibinga GH, Miyanohara A, Esko JD, et al. Cell surface heparan sulfate is a receptor for attachment of envelope protein-free retrovirus-like particles and VSV-G pseudotyped MLV-derived retrovirus vectors to target cells [J]. Mol Ther, 2002 May,5(5 Pt 1):538-46.
[68] Schulze A, Gripon P, Urban S. Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans [J]. Hepatology, 2007 Dec,46(6): 1759- 68.
[69] Leistner CM, Gruen-Bernhard S, Glebe D. Role of glycosaminoglycans for binding and infection of hepatitis B virus [J]. Cell Microbiol, 2008 Jan, 10(1): 122-33.
[70] Diao J, Slaney DM, Michalak TI. Modulation of the outcome and severity of hepadnaviral hepatitis in woodchucks by antibodies to hepatic asialoglycoprotein receptor [J]. Hepatology, 2003 Sep, 38(3):629-38.
[71] Owada T, Matsubayashi K, Sakata H. et al. Interaction between desialylated hepatitis B virus and asialoglycoprotein receptor on hepatocytes may be indispensable for viral binding and entry [J]. J Viral Hepat. 2006 Jan,13(1):11-8.
[72] Wisse E, Braet F, Luo D, et al. Structure and function of sinusoidal lining cells in the liver [J]. Toxicol Pathol, 1996, 24(1):100-11.
[73] De Falco S, Ruvoletto MG, Verdoliva A, et al. Cloning and expression of a novel hepatitis B virus-binding protein from HepG2 cells [J] . J Biol Chem, 2001 Sep 28,276(39): 36613-23.
[74] Xia HB, Chen ZY, Chen XG. Overexpression of hepatitis B virus-binding protein, squamous cell carcinoma antigen 1, extends retention of hepatitis B virus in mouse liver [J]. Acta Biochim Biophys Sin (Shanghai), 2006 Jul, 38(7):484-91.
[75] Pontisso P, Calabrese F, Benvegnu L et al. Over expression of squamous cell carcinoma antigen variants in hepatocellular carcinoma [J]. Br J Cancer,2004 Feb 23,90 (4):833-7.
[76] Beneduce L, Castaldi F, Marino M et al. Squamous cell carcinoma antigen- immunoglobulin M complexes as novel biomarkers for hepatocellular carcinoma [J]. Cancer, 2005 Jun 15,103 (12): 2558-65.
[77] Urban S. Binding of duck carboxypeptidase D to duck hepatitis B virus [J]. Methods Mol Med, 2004, 95: 199-212.
[78] Maenz C, Chang SF, Iwanski A, et al. Entry of duck hepatitis B virus into primary duckliver and kidney cells after discovery of a fusogenic region within the large surface protein [J]. J Virol, 2007 May, 81(10):5014-23.
[79] Deng Q, Zhai JW, Michel ML, et al. Identification and characterization of peptides that interact with hepatitis B virus via the putative receptor binding site [J]. J Virol, 2007 Apr, 81(8): 4244-54.
[80] Gripon P, Rumin S, Urban S, et al. Infection of a human hepatoma cell line by hepatitis B virus [J]. Proc Natl Acad Sci U S A, 2002, 99:15655-60.
[81] Glebe D, Aliakbari M, Krass P, et al. Pre-S1 antigen-dependent infection of Tupaia hepatocyte cultures with human hepatitis B virus [J]. J Virol, 2003 Sep, 77(17):9511-21.
[82] de Laat B, Derksen RH, van Lummel M,et al. Pathogenic anti-beta2-glycoprotein I antibodies recognize domain I of beta2-glycoprotein I only after a conformational change.Blood,2006, Mar 1;107(5):1916-24.
[83] Igarashi M, Matsuura E. Human beta2-glycoprotein I as an anticardiolipin cofactor determined using mutants expressed by a baculovirus system [J]. Blood, 1996 Apr 15, 87(8):3262-70.
[84] Mehdi H, Naqvi A, Kamboh MI. Recombinant hepatitis B surface antigen and anionic phospholipids share a binding region in the fifth domain of beta2-glycoprotein I (apolipoprotein H)[J]. Biochim Biophys Acta. 2008 Mar;1782(3):163-8.
[85] Alarcon-segovia D. Climical manifestations of the antiphospholipid syndrome [J]. J Rheumatol, 1992, 19:1778-81.
[86] Wang HH, Chiang AN. Cloning and characterization of the human beta2- glycoprotein I (beta2-GPI) gene promoter: roles of the atypical TATA box and hepatic nuclear factor-1 alpha in regulating beta2-GPI promoter activity [J]. Biochem J, 2004, 380:455-63.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |