Figure 3. Cxcr2 deletion in murine BM... | American Society of Hematology

$Cxcr2 deletion in murine BM improves counts and reticulin fibrosis in the hMPLW515L adoptive transfer model of MF. (A) WBC counts (×103/μL), hematocrit levels (%), and platelet counts (×103/μL) of Cxcr2f/f;Cre+ knockout (KO) hMPLW515L mice compared with Cxcr2f/f;Cre– WT hMPLW515L or MSCV-MigR1-IRES-GFP EV control mice at timed euthanization 9 weeks after transplant. N = 4 or 5 per arm; ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. Data shown represent mean ± standard error of mean (SEM). Two-way analysis of variance was used to compare groups. (B) Peripheral blood mutant cell fraction vs GFP percentage in Cxcr2f/f;Cre+ hMPLW515L mice vs Cxcr2f/f;Cre– WT hMPLW515L or EV control mice. N = 4 or 5 per arm; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. Data shown represent mean ± SEM. (C) Liver weights (mg) of Cxcr2f/f;Cre+ KO vs Cxcr2f/f;Cre– WT hMPLW515L mice compared with EV controls. ∗∗P < .01. Data shown represent mean ± SEM. (D) Representative H&E and reticulin images of BM from Cxcr2f/f;Cre+ KO vs Cxcr2f/f;Cre– WT hMPLW515L mice at timed euthanization 9 weeks after transplant. Representative images of N = 6 mice per arm. (E) Kaplan-Meier survival analysis of Cxcr2f/f;Cre+ KO hMPLW515L mice (N = 16) vs Cxcr2f/f;Cre– WT hMPLW515L mice (N = 13). ∗∗P < .01 (log-rank test). (F) Fold change in serum cytokine levels of IL-6, IL-10, and TNFα of Cxcr2f/f;Cre+ KO compared with Cxcr2f/f;Cre– WT hMPLW515L mice. N = 8 per arm. ∗P < .05. Data shown represent mean ± SEM. (G) Western blot analysis of the alarmins S100a8/a9 from the harvested splenocytes of Cxcr2f/f;Cre+ KO vs Cxcr2f/f;Cre– WT hMPLW515L mice. Original magnification ×20 (D). H&E, hematoxylin and eosin; ns, not significant.$

Figure 3.

Cxcr2 deletion in murine BM improves counts and reticulin fibrosis in the hMPL^W515L adoptive transfer model of MF. (A) WBC counts (×10³/μL), hematocrit levels (%), and platelet counts (×10³/μL) of Cxcr2^f/f;Cre⁺ knockout (KO) hMPL^W515L mice compared with Cxcr2^f/f;Cre^– WT hMPL^W515L or MSCV-MigR1-IRES-GFP EV control mice at timed euthanization 9 weeks after transplant. N = 4 or 5 per arm; ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. Data shown represent mean ± standard error of mean (SEM). Two-way analysis of variance was used to compare groups. (B) Peripheral blood mutant cell fraction vs GFP percentage in Cxcr2^f/f;Cre⁺ hMPL^W515L mice vs Cxcr2^f/f;Cre^– WT hMPL^W515L or EV control mice. N = 4 or 5 per arm; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. Data shown represent mean ± SEM. (C) Liver weights (mg) of Cxcr2^f/f;Cre⁺ KO vs Cxcr2^f/f;Cre^– WT hMPL^W515L mice compared with EV controls. ∗∗P < .01. Data shown represent mean ± SEM. (D) Representative H&E and reticulin images of BM from Cxcr2^f/f;Cre⁺ KO vs Cxcr2^f/f;Cre^– WT hMPL^W515L mice at timed euthanization 9 weeks after transplant. Representative images of N = 6 mice per arm. (E) Kaplan-Meier survival analysis of Cxcr2^f/f;Cre⁺ KO hMPL^W515L mice (N = 16) vs Cxcr2^f/f;Cre^– WT hMPL^W515L mice (N = 13). ∗∗P < .01 (log-rank test). (F) Fold change in serum cytokine levels of IL-6, IL-10, and TNFα of Cxcr2^f/f;Cre⁺ KO compared with Cxcr2^f/f;Cre^– WT hMPL^W515L mice. N = 8 per arm. ∗P < .05. Data shown represent mean ± SEM. (G) Western blot analysis of the alarmins S100a8/a9 from the harvested splenocytes of Cxcr2^f/f;Cre⁺ KO vs Cxcr2^f/f;Cre^– WT hMPL^W515L mice. Original magnification ×20 (D). H&E, hematoxylin and eosin; ns, not significant.

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