Figure 4
Figure 4. GMI-1070 alters leukocyte recruitment. (A) The rolling flux fraction was increased by nearly 2-fold in SCD mice treated with GMI-1070, whereas it was completely inhibited when both endothelial selectins were blocked by antibody administration. (B) The average number of leukocytes adherent to endothelium was significantly reduced in SCD mice treated with GMI-1070 but completely inhibited by antiselectin antibodies. (C) Representative images of venules from sickle mice treated with PBS, GMI-1070, or anti–P- and –E-selectin antibodies. Each still frame was taken at the 30-minute time point after TNF-α injection. Both small molecule selectin antagonists and antiselectin antibodies significantly reduced the number of adherent leukocytes (circles) and RBCs interacting with adherent leukocytes (black arrows; see data in Figure 5). The small white arrow indicates an RBC interaction with the endothelium, and the large white arrow shows the direction of blood flow.

GMI-1070 alters leukocyte recruitment. (A) The rolling flux fraction was increased by nearly 2-fold in SCD mice treated with GMI-1070, whereas it was completely inhibited when both endothelial selectins were blocked by antibody administration. (B) The average number of leukocytes adherent to endothelium was significantly reduced in SCD mice treated with GMI-1070 but completely inhibited by antiselectin antibodies. (C) Representative images of venules from sickle mice treated with PBS, GMI-1070, or anti–P- and –E-selectin antibodies. Each still frame was taken at the 30-minute time point after TNF-α injection. Both small molecule selectin antagonists and antiselectin antibodies significantly reduced the number of adherent leukocytes (circles) and RBCs interacting with adherent leukocytes (black arrows; see data in Figure 5). The small white arrow indicates an RBC interaction with the endothelium, and the large white arrow shows the direction of blood flow.

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