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- W2048288061 abstract "71 We previously showed that rat IP-9125 ICAM-1 antisense oligodeoxynucleotide (oligo) inhibits ICAM-1 protein expression in kidney allografts. The present study examined whether intragraft inhibition of ICAM-1 protein expression by IP-9125 blocks allograft rejection. In particular, the effect of donor pretreatment or graft perfusion with IP-9125 on kidney allograft survival was tested in rats. Pretreatment of Lewis (LEW; RT1l) donors with 10 mg/kg/day IP-9125 on three (days -2, -1, and 0) or on five (days -4, -3, -2, -1, and 0) occasions prolonged kidney allograft survivals to 15.3 ± 3.8 days (p<0.01) and 19.8 ± 2.6 days (p<0.01), respectively. In contrast, a single i.v. injection of IP-9125 (day 0) in LEW donors was ineffective (9.8 ± 1.0 days; NS). Five-day pre-treatment of donors with 10.0 mg/kg/day scrambled control IP-12140 oligo did not prolong kidney allograft survivals (9.0±0.0 days). Ex vivo kidney allograft perfusion with IP-9125 at doses of 5, 10, or 20 mg in 5 ml saline extended recipient survival rates to 14.0 ± 5.3 days (p<0.01), 19.3 ± 2.1 days (p<0.01), and 37.5 ± 7.5 days (p<0.001), respectively. In contrast, perfusion with 5.0, 10.0, or 20 mg in 5 ml saline of a scrambled control IP-12140 oligo resulted in mean survival times (MSTs) of 12.3 ± 4.2 days, 13.3 ± 6.8 days, and 12.6 ± 5.0 days, respectively (all NS). Intragraft distribution of IP-9125 was examined after perfusion of LEW kidney allografts with 10.0 mg of rhodamine-labeled IP-9125 before transplantation to ACI recipients. Immediately after perfusion, 4.25% of the total IP-9125 dose remained in the kidney, with most of this found in the extracellular space. Within 4 hours after kidney transplantation, 2.9% of the perfused IP-9125 was found in the kidney, mostly in the intracellular space-namely, in the tubular epithelium. Even 24 hours after grafting, 1.1% of the total IP-9125 dose was present in the kidney allograft. Thus, intragraft inhibition of ICAM-1 protein expression is sufficient to block organ allograft rejection. This research was funded in part by ISIS Pharmaceuticals, Carlsbad, CA." @default.
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- W2048288061 date "1998-10-01" @default.
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- W2048288061 title "INTRAGRAFT INHIBITION OF ICAM-1 EXPRESSION BY ICAM-1 ANTISENSE OLIGODEOXYNUCLEOTIDE BLOCKS KIDNEY ALLOGRAFT REJECTION" @default.
- W2048288061 doi "https://doi.org/10.1097/00007890-199810270-00101" @default.
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