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. 2018 Dec 18;49(6):1175–1190.e7. doi: 10.1016/j.immuni.2018.10.007

Figure 7.

Figure 7

Relevance of Rhythmic Leukocyte Trafficking in Inflammation, Leukemia, and Humans

(A) Blood leukocyte numbers after acute treatment without (ctrl) or with LPS in combination with functional blocking antibodies directed against the indicated molecules at ZT1 and ZT13 (n = 3–12 mice; one-way ANOVA followed by Dunnett comparison to the LPS group and unpaired Student’s t test for comparisons between ZT1 and ZT13 groups).

(B) Overview of functional blocking effects on leukocyte subsets in blood after LPS treatment targeting the indicated molecules at ZT1 and ZT13 (n = 3–12 mice; one-way ANOVA).

(C) Numbers of circulating blasts present in the blood of C57BL/6J CD45.1 recipients at midday 1 week after engraftment at ZT1 and ZT13 with mouse C1498 (AML) or BS50 (B-ALL) cells (n = 7 or 8 mice; Mann-Whitney test).

(D) Numbers of circulating blasts present in the blood of NSG recipient mice at midday 1 week after engraftment at ZT1 and ZT13 with human NALM-6 B-ALL cells (n = 8 mice; unpaired Student’s t test).

(E) Oscillation of blood B cell numbers in human blood (n = 8 subjects; repeated-measures one-way ANOVA).

(F) CXCR4 expression on human B cells over 24 hr (n = 8 subjects; repeated-measures one-way ANOVA).

(G) Transendothelial migration (TEM) capacity of human primary B cells harvested from three donors at 11 a.m. and 7 p.m. across HUVECs. Numbers are normalized to 11 a.m. levels (n = 4 assays; unpaired Student’s t test).

(H and I) Blocking efficacy of AMD3100 (H) or an anti-LFA-1 antibody (I) on TEM capacity of human primary B cells harvested at 11 a.m. and 7 p.m. Numbers are normalized to and compared with those of vehicle and isotype controls, respectively (n = 3 donors; unpaired Student’s t test).

(J and K) Example of the TEM capacity of human B cells from one patient at 11 a.m. and 7 p.m. after AMD3100 (J) or anti-LFA-1 treatment (K) plotted over time (n = 4 assays; two-way ANOVA with Tukey post-test).

∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001; #, ##, ###, #### indicate significance levels analogous to those of the LPS groups. All data are represented as mean ± SEM. ns, not significant. See also Figure S7.