Severe fibrosis in hepatitis C virus-infected patients is associated with increased activity of the mannan-binding lectin (MBL)/MBL-associated serine protease 1 (MASP-1) complex

被引:30
作者
Brown, K. S.
Keogh, M. J.
Tagiuri, N.
Grainge, M. J.
Presanis, J. S.
Ryder, S. D.
Irving, W. L.
Ball, J. K.
Sim, R. B.
Hickling, T. P. [1 ]
机构
[1] Univ Nottingham, Inst Infect Immun & Inflammat, Sch Mol Med Sci, Queens Med Ctr, Nottingham NG7 2UH, England
[2] Univ Nottingham, Div Epidemiol & Publ Hlth, Sch Community Hlth Sci, Queens Med Ctr, Nottingham NG7 2UH, England
[3] Univ Oxford, Dept Biochem, MRC, Immunochem Unit, Oxford OX1 3QU, England
[4] Queens Med Ctr, Dept Med, Directorate Med, Nottingham NG7 2UH, England
关键词
fibrogenesis; HCV; innate immunity; mannan-binding lectin; mannan-binding lectin associated serine protease-1;
D O I
10.1111/j.1365-2249.2006.03264.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mannan-binding lectin (MBL) binds microorganisms via interactions with glycans on the target surface. Bound MBL subsequently activates MBL-associated serine protease proenzymes (MASPs). A role for MBL in hepatitis C virus (HCV) infection had been indicated by previous studies examining MBL levels and polymorphisms in relation to disease progression and response to treatment. We undertook this study to investigate a possible relationship between disease progression and functional MBL/MASP-1 complex activity. A functional assay for MBL/MASP-1 complex activity was employed to examine serum samples from patients with chronic HCV infection, non-HCV liver disease and healthy controls. Intrapatient consistency of MBL/MASP-1 complex activity levels was assessed in sequential samples from a subgroup of patients. Median values of MBL/MASP-1 complex activity were higher in sera from patients with liver disease compared with healthy controls. MBL/MASP-1 complex activity levels correlate with severity of fibrosis after adjusting for confounding factors (P = 0.003). MBL/MASP-1 complex activity was associated more significantly with fibrosis than was MBL concentration. The potential role of MBL/MASP-1 complex activity in disease progression is worthy of further study to investigate possible mechanistic links.
引用
收藏
页码:90 / 98
页数:9
相关论文
共 43 条
[1]   Natural substrates and inhibitors of mannan-binding lectin-associated serine protease-1 and-2:: A study on recombinant catalytic fragments [J].
Ambrus, G ;
Gál, P ;
Kojima, M ;
Szilágyi, K ;
Balczer, J ;
Antal, J ;
Gráf, L ;
Laich, A ;
Moffatt, BE ;
Schwaeble, W ;
Sim, RB ;
Závodszky, P .
JOURNAL OF IMMUNOLOGY, 2003, 170 (03) :1374-1382
[2]   The glycosylation of human serum IgD and IgE and the accessibility of identified oligomannose structures for interaction with mannan-binding lectin [J].
Arnold, JN ;
Radcliffe, CM ;
Wormald, MR ;
Royle, L ;
Harvey, DJ ;
Crispin, M ;
Dwek, RA ;
Sim, RB ;
Rudd, PM .
JOURNAL OF IMMUNOLOGY, 2004, 173 (11) :6831-6840
[3]   Identification of a site on mannan-binding lectin critical for enhancement of phagocytosis [J].
Arora, M ;
Munoz, E ;
Tenner, AJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (46) :43087-43094
[4]   Intrahepatic gene expression during chronic hepatitis C virus infection in chimpanzees [J].
Bigger, CB ;
Guerra, B ;
Brasky, KM ;
Hubbard, G ;
Beard, MR ;
Luxon, BA ;
Lemon, SM ;
Lanford, RE .
JOURNAL OF VIROLOGY, 2004, 78 (24) :13779-13792
[5]   Mannose binding lectin gene polymorphisms confer a major risk for severe infections after liver transplantation [J].
Bouwman, LH ;
Roos, A ;
Terpstra, OT ;
De Knijff, P ;
Van Hoek, B ;
Verspaget, HW ;
Berger, SP ;
Daha, MR ;
Frölich, M ;
Van Der Slik, AR ;
Doxiadis, II ;
Roep, BO ;
Schaapherder, AFM .
GASTROENTEROLOGY, 2005, 129 (02) :408-414
[6]   Mannose-binding lectin (MBL) mutants are susceptible to matrix metalloproteinase proteolysis - Potential role in human MBL deficiency [J].
Butler, GS ;
Sim, D ;
Tam, E ;
Devine, D ;
Overall, CM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (20) :17511-17519
[7]   Mannose-binding lectin in chronic hepatitis B virus infection [J].
Chong, WP ;
To, YF ;
Ip, WK ;
Yuen, MF ;
Poon, TP ;
Wong, WHS ;
Lai, CL ;
Lau, YL .
HEPATOLOGY, 2005, 42 (05) :1037-1045
[8]   Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis [J].
Corpechot, C ;
Barbu, V ;
Wendum, D ;
Kinnman, N ;
Rey, C ;
Poupon, R ;
Housset, C ;
Rosmorduc, O .
HEPATOLOGY, 2002, 35 (05) :1010-1021
[9]   MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway [J].
Dahl, MR ;
Thiel, S ;
Matsushita, M ;
Fujita, T ;
Willis, AC ;
Christensen, T ;
Vorup-Jensen, T ;
Jensenius, JC .
IMMUNITY, 2001, 15 (01) :127-135
[10]   The natural course of hepatitis C virus infection 18 years after an epidemic outbreak of non-A, non-B hepatitis in a plasmapheresis centre [J].
Datz, C ;
Cramp, M ;
Haas, T ;
Dietze, O ;
Nitschko, H ;
Froesner, G ;
Muss, N ;
Sandhofer, F ;
Vogel, W .
GUT, 1999, 44 (04) :563-567