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T. Yokokawa et al.
derived macrophages were higher than those in the WT BM-derived macrophages (Figure 6B). Ruxolitinib, a selec- tive JAK1/2 inhibitor, significantly decreased both Mmp2 and Mmp9 expression levels in the JAK2V617F macrophages (Figure 6C). These data suggest that BM-derived macrophages carrying JAK2 V617F play important roles in the genesis of MMP.
A
Inhibition of JAK1/2 with ruxolitinib prevents hematopoietic JAK2 V617F-induced abdominal aortic aneurysm formation
We investigated whether inhibition of JAK1/2 could attenuate hematopoietic JAK2 V617F-induced AAA for- mation (Figure 7A). Ruxolitinib treatment significantly decreased white blood cell counts and spleen weights in
B
Figure 3. Hematopoietic JAK2 V617F increases inflammatory cell infiltration in the abdominal aorta. (A) Representative immunohistochemical images of the aorta stained by anti-CD45, CD68, and Ly6B.2 antibodies in the WT-BMT mice and JAK2V617F-BMT mice 4 weeks after saline or angiotensin II infusion. Arrows indicate Ly6B.2-positive cells. Scale bars, 50 mm. (B) Quantitative analyses of the CD45+ (n=5–6), CD68+ (n=3–5), and Ly6B.2+ (n= 3–5) cells in the aortic sections. All data are presented as mean ± standard error of the mean. *P<0.05 vs. the corresponding saline-infused mice and †P <0.05 vs. the Ang II-infused WT-BMT mice by one- way ANOVA with Tukey post-hoc analysis. WT, ApoE−/−: mice transplanted with bone marrow (BM) cells from wild-type (WT) mice; JAK2V617F, ApoE−/−: mice transplanted with BM cells from JAK2V617F mice; BMT: BM transplantation; Ang II: angiotensin II.
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haematologica | 2021; 106(7)