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
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共 11 条
  • [1] 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
  • [2] M-T7, a viral chemokine binding protein, blocks plaque growth after stent implant in a rabbit angioplasty model
    Dai, E
    Pflugfelder, PW
    Liu, LY
    Kidwai, B
    White, J
    Macaulay, C
    McFadden, G
    Christov, A
    Leibbrandt, M
    Lucas, AR
    [J]. CIRCULATION, 2001, 104 (17) : 90 - 90
  • [3] M-T7, a viral chemokine modulating protein (vCMP) inhibits plaque growth through interruption of chemokine: GAG interactions
    Dai, Erbin
    Liu, Liying
    Viswanathan, Kasinath
    Ramanujam, Ganesh Munuswamy
    Macauley, Colin
    Li, Xing
    Esko, Jeffrey D.
    Charo, Israel F.
    McFadden, Grant
    Lucas, Alexandra
    [J]. CIRCULATION, 2006, 114 (18) : 259 - 259
  • [4] M-T7, a viral chemokine binding protein, blocks early inflammatory responses to angioplasty-induced injury and subsequent development of intimal plaque in a rat model
    Liu, L
    Dai, E
    Lalani, AS
    Seet, B
    McCauley, C
    McFadden, G
    Lucas, A
    [J]. CIRCULATION, 1999, 100 (18) : 614 - 614
  • [5] Viral chemokine modulating protein, M-T7, interrupts chemokine: Glycosaminoglycan (GAG) interaction: M-T7 inhibitory activity is dependent upon Y46 and V210 aminoacid residues
    Dai, Erbin
    McIvor, Dana
    Liu, Liying
    Munaswamy-Ramanujam, Ganesh
    Sun, Yunming
    Esko, Jeffrey
    Charo, Israel F.
    McFadden, Grant
    Lucas, Alexandra
    [J]. CIRCULATION, 2007, 116 (16) : 208 - 208
  • [6] SDZ-RAD prevents manifestation of chronic rejection in rat renal allografts
    Viklicky, O
    Zou, HQ
    Müller, V
    Lacha, J
    Szabó, A
    Heemann, U
    [J]. TRANSPLANTATION, 2000, 69 (04) : 497 - 502
  • [7] PG490-88, a new immunosuppressant, effectively prevents acute and chronic rejection in rat renal allografts
    Pan, F
    Fisniku, O
    Wynn, C
    Erickson, LM
    Crews, G
    Jang, MS
    Sudo, Y
    Tamura, K
    Kobayashi, M
    Benediktsson, H
    Jiang, H
    [J]. TRANSPLANTATION PROCEEDINGS, 2005, 37 (01) : 134 - 136
  • [8] PG490-88, a novel immunosuppressant, effectively prevents acute and chronic rejection in rat renal allografts.
    Pan, F
    Fisniku, O
    Wynn, C
    Erickson, LM
    Crews, G
    Jang, MS
    Sudo, Y
    Tamura, K
    Kobayashi, M
    Benediktsson, H
    Jiang, HS
    [J]. AMERICAN JOURNAL OF TRANSPLANTATION, 2004, 4 : 193 - 193
  • [9] Defining the anti-inflammatory activity of a potent myxomaviral chemokine modulating protein, M-T7, through site directed mutagenesis
    Bartee, M. Y.
    Chen, H.
    Dai, E.
    Liu, L. Y.
    Davids, J. A.
    Lucas, A.
    [J]. CYTOKINE, 2014, 65 (01) : 79 - 87
  • [10] Transplant Vasculopathy Response in CCR2 and NDST-1 Deficient Mice Aortic Transplant Model After Viral Anti-Inflammatory Chemokine Modulating Protein, M-T7, Treatment
    Dai, Erbin
    Liu, Liying
    Bartee, Mee
    McIvor, Dana
    Sun, Yun Ming
    Macaulay, Colin
    Esko, Jeffrey D.
    Charo, Israel
    Lucas, Alexandra R.
    [J]. CIRCULATION, 2009, 120 (18) : S1029 - S1029