IVIG prevents both the interactions between sickle RBCs and WBCs and vaso-occlusion in sickle cell mice. (A) IVIG reduces RBC-WBC interactions in vivo in a dose-dependent manner; differences were significant for the groups treated with IVIG at 200 mg/kg or more. #P ≤ .01 compared with PBS, P < .05 compared with the albumin-treated group. (B) IVIG 400 mg/kg improves centerline RBC velocities (VRBC) in venules as measured during IVM 1 in real time using an optical Doppler velocimeter (Texas A&M, College Station), and the effect is sustained after TNF-α (IVM 2). *P < .05 compared with the albumin group. #P< .05 compared with both the PBS and albumin groups. ¶Groups in which the numbers of live mice and venules were too small for reliable determination. (C) Representative still frames after TNF-α administration of venules from sickle cell mice treated with 1 mg/kg or 400 mg/kg IVIG. In venules of sickle mice treated with low-dose IVIG, there are numerous interactions between RBCs (black arrows) and adherent WBCs (white arrows) accompanied by drastic reductions in blood flow in most venules. Fewer RBC-WBC interactions and adherent WBCs are observed in sickle mice treated with high-dose IVIG. Scale bar indicates 10 μm. Movie segments corresponding to these still frames (C-D) can be viewed on the Blood website. See the Supplemental Video link at the top of the online article.
