Figure 5
Inhibition of murine collagen-induced arthritis by Tie1-751. On the day of arthritis onset, mice received intravenously 1 × 107 plaque-forming units of adenoviruses expressing either LacZ (○) or Tie1-751 alternative splice variants (ASV) (●), or remained untreated (□) as indicated. (a) Clinical score was recorded daily, and data were analyzed by two-way analysis of variance versus untreated mice. LacZ, not significant (P = 0.3734); Tie1-751, P < 0.001; n = 6 per group. (b) Paw swelling was recorded using calipers daily, and data were analyzed by two-way analysis of variance versus untreated mice. LacZ, not significant (P = 0.5134); Tie1-751, P < 0.001. Data are means of n = 6. (c) Serial sections of mouse hind feet were stained with either H & E (left panels) or toluidine blue (right panels). Figure shows tibia–tarsus joint sections from untreated mice (top panels), from LacZ adenovirus-treated mice (middle panels), and from Tie1-751 ASV adenovirus-treated mice (bottom panels). Sections are shown at 40× magnification; scale bar = 20 μm. (d) Pharmacokinetics of Tie1-751 from the ASV-expressing adenovirus. Sera from untreated mice or mice treated intravenously with 1 × 109 plaque-forming units of Tie1-751 ASV adenovirus were analyzed after the indicated times by western blot, followed by scanning and quantitation using Tie1-751 standard. (e) Effect of recombinant Tie1-751-Fc protein on clinical score. Results are from mice on day 10 of arthritis. Filled bars, untreated mice; empty bars, mice treated with recombinant Tie1-751-Fc 30 mg/kg, three times weekly. Data are means of n = 6. **P < 0.01 for Tie-751-Fc treated mice versus untreated mice.