Gene transfer into inflamed glomeruli using macrophages transfected with adenovirus

被引:30
作者
Kluth, DC [1 ]
Erwig, LP [1 ]
Pearce, WP [1 ]
Pees, AJ [1 ]
机构
[1] Univ Aberdeen, Dept Med & Therapeut, Aberdeen AB25 2ZD, Scotland
关键词
macrophages; recombinant adenovirus; interleukin-4; nitric oxide; glomerulonephritis;
D O I
10.1038/sj.gt.3301060
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In vivo gene transfer to sites of inflammatory disease provides a novel method both for studying the effects of cytokines and growth factors, and for therapeutic intervention. Macrophages play a pivotal role in the development and control of inflammation and are therefore logical cells to use for genetic modification and in vivo gene delivery. In this study we show that macrophages (both cell lines and primary cultures) can be transfected by recombinant adenoviruses expressing p-galactosidase, that the macrophages become activated by the transfection process as determined by generation of nitric oxide and can be easily manipulated to localise to inflamed glomeruli after direct injection into the renal artery of rats with an experimentally induced glomerular inflammation caused by nephrotoxic nephritis. The injection of transfected macrophages reduces the severity of injury in this model of glomerulonephritis as shown by a reduction in the degree of albuminuria. This approach provides a favourable system for gene delivery in inflammatory disease and shows that both the functional properties of the transfected macrophage as well the transgene if is engineered to produce are relevant for in vivo gene transfer.
引用
收藏
页码:263 / 270
页数:8
相关论文
共 52 条
  • [1] Ajuebor MN, 1999, J IMMUNOL, V162, P1685
  • [2] THE SPECIFIC RECOGNITION BY MACROPHAGES OF CD8(+),CD45RO(+) T-CELLS UNDERGOING APOPTOSIS - A MECHANISM FOR T-CELL CLEARANCE DURING RESOLUTION OF VIRAL-INFECTIONS
    AKBAR, AN
    SAVILL, J
    GOMBERT, W
    BOFILL, M
    BORTHWICK, NJ
    WHITELAW, F
    GRUNDY, J
    JANOSSY, G
    SALMON, M
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (05) : 1943 - 1947
  • [3] Bellingan GJ, 1996, J IMMUNOL, V157, P2577
  • [4] Bondeson J, 1999, J IMMUNOL, V162, P2939
  • [5] THE USE OF BETA-GALACTOSIDASE AS A TRACER IN IMMUNOCYTOCHEMISTRY
    BONDI, A
    CHIEREGATTI, G
    EUSEBI, V
    FULCHERI, E
    BUSSOLATI, G
    [J]. HISTOCHEMISTRY, 1982, 76 (02) : 153 - 158
  • [6] MACROPHAGE ENGULFMENT OF APOPTOTIC NEUTROPHILS CONTRIBUTES TO THE RESOLUTION OF ACUTE PULMONARY INFLAMMATION IN-VIVO
    COX, G
    CROSSLEY, J
    XING, Z
    [J]. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1995, 12 (02) : 232 - 237
  • [7] MIP-1α as a critical macrophage chemoattractant in murine wound repair
    DiPietro, LA
    Burdick, M
    Low, QE
    Kunkel, SL
    Strieter, RM
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (08) : 1693 - 1698
  • [8] Erwig LP, 1998, J IMMUNOL, V161, P1983
  • [9] Receptor-mediated gene transfer into macrophages
    Ferkol, T
    Perales, JC
    Mularo, F
    Hanson, RW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (01) : 101 - 105
  • [10] Direct adenovirus-mediated gene transfer of interleukin 1 and tumor necrosis factor α soluble receptors to rabbit knees with experimental arthritis has local and distal anti-arthritic effects
    Ghivizzani, SC
    Lechman, ER
    Kang, R
    Tio, C
    Kolls, J
    Evans, CH
    Robbins, PD
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (08) : 4613 - 4618