VEGF-A165 increases MK migration to vascular niche via a CXCR4-dependent process. Prolonged CXCR4 antagonism suppresses VEGF-A165–induced thrombocytosis. Mice were administered either VEGF-A165 (100 μg/kg intraperitoneally) or vehicle (PBS) each day for 4 consecutive days. Some groups of mice were administered a CXCR4 antagonist (AMD3100 5 mg/kg) or PBS b.i.d. (bis in die: twice-daily dosing) for the 4 days of VEGF-A165 treatment. Femurs were excised for bone marrow histology, stained with toluidine blue, and then analyzed for the number of MKs (A) per field of view and (B) adjacent to sinusoidal vessels. (C) Circulating platelet numbers were enumerated 24 hours after last growth factor administration. Data are expressed as mean ± SEM; n = 5-6 animals per group; **P < .01 and ***P < .001 compared with control or as indicated compared with control.
