Dietary ironrestriction amelioratesacute VOE in SCD mice. (A) Schematic experimental design for iron diet treatments. (B) Non-heme iron content of the bone marrow (N = 5), spleen (N = 5), and liver (N = 5), and serum iron concentration (N = 10) are decreased after dietary iron restriction. (C) WBC count, (D) RBC count, and total hemoglobin (HGB) concentration in Ctrl and IRD SCD mice (N = 14-15). (E) Mean corpuscular hemoglobin concentration (MCHC), MCH, mean corpuscular volume in Ctrl and IRD mice (merged data from 3 experiments, N = 14-15). (F) Serum soluble adhesion molecules (sP-selectin, sE-selectin, sVcam-1 and sIcam-1) by enzyme-linked immunosorbent assay (N = 10). (G) FACS plots with gating strategy and quantification of CXCR4^Hi CD62^Lo aged neutrophils in Ctrl and IRD mice. (H) Intravital microscopy images of inflamed cremasteric venules in Ctrl and IRD mice. Scale bars, 10 μm. (I) Cremasteric venule diameters, (J) red cell velocity (V_rbc), (K) blood flow rate, (L) the number of adherent leukocytes (N = 41-47), and (M) survival rate after TNF-α injection (N = 9) are compared between Ctrl and IRD mice. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001.