Gene transfer into inflamed glomeruli using macrophages transfected with adenovirus

In vivo gene transfer to sites of inflammatory disease provides a novel met hod both for studying the effects of cytokines and growth factors, and for therapeutic intervention. Macrophages play a pivotal role in the developmen t and control of inflammation and are therefore logical cells to use for ge netic modification and in vivo gene delivery. In this study we show that ma crophages (both cell lines and primary cultures) can be transfected by reco mbinant adenoviruses expressing p-galactosidase, that the macrophages becom e activated by the transfection process as determined by generation of nitr ic oxide and can be easily manipulated to localise to inflamed glomeruli af ter direct injection into the renal artery of rats with an experimentally i nduced glomerular inflammation caused by nephrotoxic nephritis. The injecti on 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 inflammato ry 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.