Fig. 2.
Inhibition of VEGFR1, but not VEGFR2, after myelosuppression, results in delayed hematopoietic recovery and increased mortality of the treated mice. a and b, Myelosuppression was induced by a single dose of 5FU. 12 5FU-treated BALB/c mice in each group were injected i.p. with neutralizing doses of anti-VEGFR1 (
), anti-VEGFR2 (●) or IgG control (○) in 2-d intervals starting from day 0. Mice were also treated with anti-VEGFR1 (□) and anti-VEGFR2 (◇) alone. a, WBCs were quantified. b, Survival rate was monitored on a daily basis. Survival rate was lower in the VEGFR1-treated versus IgG-treated mice (*, P < 0.001). c and d, Hematopoietic recovery following a single dose of 5FU on day 0 (c) or total body irradiation (TBI) plus carboplatin at day 0 (d) (n = 6 for both) followed by a single dose of either Ad-PlGF (
) or Ad-null (○) on day 0. d, Recombinant G-CSF (injected subcutaneously day 0–14, ■) promotes rapid hematopoietic reconstitution. Extent and duration of less than 2000/μl WBCs was significantly shorter in the Ad-PlGF-treated versus Ad-null-treated 5FU- and carboplatin/irradiation-treated mice. c, *, P < 0.001; d, *, P < 0.005. Error bars represent mean ± s.e.m. for 6–10 mice per group. e–g, H&E staining of BM sections of 5FU-treated mice 10 d after co-injection with neutralizing anti-VEGFR1 (f), anti-VEGFR2 (g) or IgG controls (e). Magnification, × 100. h–m, vWF staining of BM sections 10 d after 5FU treatment in antibody-treated mice (anti-VEGFR1 (i and l), anti-VEGFR2 (j and m) or IgG controls (h and k); megakaryocytes are depicted by arrows). Magnifications, ×100 (h–j); ×400 (k–m).