Chemokine-binding viral protein M-T7 prevents chronic rejection in rat renal allografts

被引:33
作者
Bédard, ELR
Kim, P
Jiang, JF
Parry, N
Liu, LY
Wang, H
Garcia, B
Li, X
McFadden, G
Lucas, A
Zhong, R
机构
[1] Univ Western Ontario, London Hlth Sci Ctr, Dept Surg, London, ON N6A 5A5, Canada
[2] London Hlth Sci Ctr, Multi Organ Transplant Program, London, ON, Canada
[3] John P Robarts Res Inst, London, ON N6A 5K8, Canada
[4] Viron Therapeut Inc, London, ON, Canada
[5] Univ Western Ontario, Dept Microbiol & Immunol, London, ON N6A 5A5, Canada
关键词
D O I
10.1097/01.TP.0000061604.57432.E3
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
M-T7 is a myxoma virus-encoded protein that has been found to bind and disrupt human chemokine gradients. This study examined whether purified M-T7 could prevent chronic rejection in a rat renal allograft model. Fisher F344 renal allografts were transplanted into Lewis rats. Recipients were randomly grouped into two groups: control animals treated with cyclosporine alone and animals treated with cyclosporine combined with low-, medium- and high-dose M-T7 viral protein. The survival rate was not significantly different between allograft groups. Renal allografts treated with high-dose M-T7 demonstrated a significant reduction in tubular atrophy, glomerular atrophy, vascular hyalinization, cortical scarring, and lymphocyte infiltration. Morphometric analyses demonstrated that the high-dose M-T7 group also showed a significantly decreased amount of glomerulosclerosis and transplant arteriosclerosis. These data demonstrate for the first time that the immunoregulatory viral protein M-T7 can effectively attenuate chronic rejection in rat renal allografts.
引用
收藏
页码:249 / 252
页数:4
相关论文
共 10 条
  • [1] The role of the CC chemokine, RANTES, in acute lung allograft rejection
    Belperio, JA
    Burdick, MD
    Keane, MP
    Xue, YY
    Lynch, JP
    Daugherty, BL
    Kunkel, SL
    Strieter, RM
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 165 (01) : 461 - 472
  • [2] Gene transfer of virally encoded chemokine antagonists vMIP-II and MC148 prolongs cardiac allograft survival and inhibits donor-specific immunity
    DeBruyne, LA
    Li, K
    Bishop, DK
    Bromberg, JS
    [J]. GENE THERAPY, 2000, 7 (07) : 575 - 582
  • [3] FAIRCHILD RL, 2000, GRAFT S, V3, P24
  • [4] Targeting of the chemokine receptor CCR1 suppresses development of acute and chronic cardiac allograft rejection
    Gao, W
    Topham, PS
    King, JA
    Smiley, ST
    Csizmadia, V
    Lu, B
    Gerard, CJ
    Hancock, WW
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (01) : 35 - 44
  • [5] Glycosaminoglycans mediate cell surface oligomerization of chemokines
    Hoogewerf, AJ
    Kuschert, GSV
    Proudfoot, AEI
    Borlat, F
    ClarkLewis, I
    Power, CA
    Wells, TNC
    [J]. BIOCHEMISTRY, 1997, 36 (44) : 13570 - 13578
  • [6] Evasion and exploitation of chemokines by viruses
    Lalani, AS
    McFadden, G
    [J]. CYTOKINE & GROWTH FACTOR REVIEWS, 1999, 10 (3-4) : 219 - 233
  • [7] The purified myxoma virus gamma interferon receptor homolog M-T7 interacts with the heparin-binding domains of chemokines
    Lalani, AS
    Graham, K
    Mossman, K
    Rajarathnam, K
    ClarkLewis, I
    Kelvin, D
    McFadden, G
    [J]. JOURNAL OF VIROLOGY, 1997, 71 (06) : 4356 - 4363
  • [8] Secreted poxvirus chemokine binding proteins
    Lalani, AS
    McFadden, G
    [J]. JOURNAL OF LEUKOCYTE BIOLOGY, 1997, 62 (05) : 570 - 576
  • [9] The viral anti-inflammatory chemokine-binding protein M-T7 reduces intimal hyperplasia after vascular injury
    Liu, LY
    Lalani, A
    Dai, EB
    Seet, B
    Macauley, C
    Singh, R
    Fan, L
    McFadden, G
    Lucas, A
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (11) : 1613 - 1621
  • [10] New strategies for chemokine inhibition and modulation - You take the high road and I'll take the low road
    McFadden, G
    Kelvin, D
    [J]. BIOCHEMICAL PHARMACOLOGY, 1997, 54 (12) : 1271 - 1280