Visualization of MKs in bone marrow sections from mice treated with VEGF-A165 or vehicle and CXCR4 antagonist. 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. Twenty-four hours after final AMD3100 administration, femurs were excised for bone marrow histology. (A) Representative photomicrograph of bone marrow stained with toluidine blue reveal the distribution of sinusoidal vessels (Sv) and MKs (Mk) from a PBS-treated mouse. (B-C) Higher-power magnification of femurs from PBS-treated mice showing localization of MKs in relation to sinusoidal vessels and the stroma. (D-F) Representative photomicrographs of bone marrow from a PBS + CXCR4 antagonist–treated mouse reveals a similar distribution pattern of MKs within the bone marrow stroma to that of PBS-treated mice. (G) Representative photomicrograph of bone marrow from VEGF-A165 + PBS–treated mouse reveals a more pronounced localization of MKs to sinusoidal vessels. (H-I) Higher-power confirmation of MK localized directly adjacent to sinusoidal vessels. (J-L) Representative photomicrographs of bone marrow from VEGF-A165 + CXCR4 antagonist–treated mouse reveals MKs distributed within the bone marrow stroma, with the occasional MK adjacent to a sinusoidal vessel. (A,D,G,J) Magnification: ×40. (B,C,E,F,H,I,K,L) Magnification: ×100. Photomicrographs at ×100 magnification have been turned 90° using Microsoft Powerpoint (to allow photomicrographs to fit inside figure). Bar represents 50 μm.
