Gene transfer into inflamed glomeruli using macrophages transfected with adenovirus

D C Kluth, L P Erwig, W P Pearce, A J Pees

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)263-270
Number of pages8
JournalGene Therapy
Volume7
Publication statusPublished - 2000

Keywords

  • macrophages
  • recombinant adenovirus
  • interleukin-4
  • nitric oxide
  • glomerulonephritis
  • NECROSIS-FACTOR-ALPHA
  • IN-VIVO
  • HUMAN MONOCYTES
  • WOUND REPAIR
  • NITRIC-OXIDE
  • RAT-KIDNEY
  • INFLAMMATION
  • CELLS
  • RESOLUTION
  • EXPRESSION

Cite this

Kluth, D. C., Erwig, L. P., Pearce, W. P., & Pees, A. J. (2000). Gene transfer into inflamed glomeruli using macrophages transfected with adenovirus. Gene Therapy, 7, 263-270.

Gene transfer into inflamed glomeruli using macrophages transfected with adenovirus. / Kluth, D C ; Erwig, L P ; Pearce, W P ; Pees, A J .

In: Gene Therapy, Vol. 7, 2000, p. 263-270.

Research output: Contribution to journalArticle

Kluth, DC, Erwig, LP, Pearce, WP & Pees, AJ 2000, 'Gene transfer into inflamed glomeruli using macrophages transfected with adenovirus', Gene Therapy, vol. 7, pp. 263-270.
Kluth, D C ; Erwig, L P ; Pearce, W P ; Pees, A J . / Gene transfer into inflamed glomeruli using macrophages transfected with adenovirus. In: Gene Therapy. 2000 ; Vol. 7. pp. 263-270.
@article{f11170a8b8ba4ababb057be9d55e2d9b,
title = "Gene transfer into inflamed glomeruli using macrophages transfected with adenovirus",
abstract = "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.",
keywords = "macrophages, recombinant adenovirus, interleukin-4, nitric oxide, glomerulonephritis, NECROSIS-FACTOR-ALPHA, IN-VIVO, HUMAN MONOCYTES, WOUND REPAIR, NITRIC-OXIDE, RAT-KIDNEY, INFLAMMATION, CELLS, RESOLUTION, EXPRESSION",
author = "Kluth, {D C} and Erwig, {L P} and Pearce, {W P} and Pees, {A J}",
year = "2000",
language = "English",
volume = "7",
pages = "263--270",
journal = "Gene Therapy",
issn = "0969-7128",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Gene transfer into inflamed glomeruli using macrophages transfected with adenovirus

AU - Kluth, D C

AU - Erwig, L P

AU - Pearce, W P

AU - Pees, A J

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

KW - macrophages

KW - recombinant adenovirus

KW - interleukin-4

KW - nitric oxide

KW - glomerulonephritis

KW - NECROSIS-FACTOR-ALPHA

KW - IN-VIVO

KW - HUMAN MONOCYTES

KW - WOUND REPAIR

KW - NITRIC-OXIDE

KW - RAT-KIDNEY

KW - INFLAMMATION

KW - CELLS

KW - RESOLUTION

KW - EXPRESSION

M3 - Article

VL - 7

SP - 263

EP - 270

JO - Gene Therapy

JF - Gene Therapy

SN - 0969-7128

ER -