Impact of Ang-1 signaling on peripheral-blood counts. (A) Enforced Ang-1 expression stimulates hematopoiesis and restores platelet counts in Thpo–/– mice. Both wild-type and Thpo–/– mice received a single intravenous dose of AdAng-1 (109 pfu) or AdNull (109 pfu). Ang-1 induced a delayed, but sustained, leukocytosis and thrombocytosis with an almost 2-fold increase in total white blood cell counts (top) over baseline levels in wild-type mice (n = 4, P < .05 on day 17). This effect is reproducible independent of thrombopoietin, as injection of AdAng1 into Thpo–/– mice enhanced platelet production (bottom; n = 4, P < .05 at day 17). Data are expressed as the mean ± SEM. (B) Ad-Ang1 rescues neutropenia after 5-FU. Wild-type mice (n = 4 in each group) were injected with 250 mg/kg 5-FU and received either a single tail-vein injection of AdAng-1 (109 pfu) or AdNull (109 pfu). Whereas the nadirs of platelets (top), total white blood cells (middle), and neutrophils (bottom) were not changed, Ad-Ang1 lead to a significantly accelerated recovery of total white blood cells and neutrophils (P < .05 at day 14 after 5-FU). Platelet levels showed an exaggerated rebound thrombocytosis.
