Gene transfer into inflamed glomeruli using macrophages transfected with adenovirus.
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 beta-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 it is engineered to produce are relevant for in vivo gene transfer. Gene Therapy (2000) 7, 263-270.
Kluth
D C
DC
Department of Medicine and Therapeutics, University of Aberdeen, IMS Building, Forresterhill, Aberdeen AB25 2ZD, UK.
Erwig
L P
LP
Pearce
W P
WP
Rees
A J
AJ
D000256:Adenoviridae / Q000235:genetics*; D000419:Albuminuria; D000818:Animals; D002460:Cell Line; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005921:Glomerulonephritis / Q000628:therapy; D007678:Kidney Glomerulus / Q000502:physiology; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology; D051381:Rats; D014162:Transfection / Q000379:methods*