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 language | English |
|---|---|
| Pages (from-to) | 263-270 |
| Number of pages | 8 |
| Journal | Gene Therapy |
| Volume | 7 |
| Publication status | Published - 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
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 journal › Article
}
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 -