Figure 6.
Impaired response of dnTCF4 mice to emergency granulopoiesis. (A) Schematic representation of the experimental setup. WT and dnTCF4 mice were injected intraperitoneally (i.p.) with 35 μg of LPS at t = 0 and t = 48 hours. Analysis was performed 24 hours after last injection. (B) Percentage of CD11b+ Ly6Ghi cells in PB of WT and dnTCF4 mice treated with PBS or LPS. Each group contained at least 8 animals from 2 independent experiments. (C) Number of neutrophils per liter (L) in PB based on an auto hematology analyzer. WT and dnTCF4 mice were treated with PBS or LPS as indicated. At least 5 mice were included in each group. (D) Percentage of CD11b+ Ly6Ghi cells in BM of WT and dnTCF4 mice treated with PBS or LPS. Each group contained at least 6 animals from 2 independent experiments. (E) Percentage of immature granulocytes (CD11b+ Ly6Glo) in BM of WT and dnTCF4 mice treated with PBS or LPS. Each group contained at least 6 animals from 2 independent experiments. Quantification of (F) c-Kit+ cells and (G) myeloid progenitors in BM from WT and dnTCF4 mice. The y-axes indicate the fold increase from PBS to LPS treatment; n = 5-6 animals from 2 independent experiments. (H) Kaplan-Meier survival analysis of WTT (n = 12) and dnTCF4 (n = 14) mice that were intravenously injected with 2 consecutive doses of Candida albicans (5 × 105 CFU at experimental days 0 and 25). Mantle-Cox test was used to assess statistical significance of obtained results (P = .0413). (I) Schematic representation of the experimental setup. WT and dnTCF4 mice were injected intraperitoneally (i.p.) with 150 mg/kg 5-FU as indicated (black arrows). The y-axis indicates duration of the experiment in days. (J) Number of neutrophils per liter (L) in PB based on auto hematology analyzer. WT and dnTCF4 mice were treated with 1 injection of 5-FU. Y-axis indicates days of analysis; n = 7. (K) WT and dnTCF4 relative weight upon 5-FU treatment as indicated in panel I. The y-axis indicates the percentage of initial weight (day 0). The x-axis shows days of treatment as indicated in panel I. (L) Kaplan-Meier survival analysis of WTT (n = 4) and dnTCF4 (n = 4) mice intravenously injected with 5-FU as indicated in panel I. Mantle-Cox test was used to assess statistical significance of obtained results (P = .0401). Data in Figure 6 represent mean ± SD, and unless otherwise indicated, 2-tailed Student t test was used to assess statistical significance (*P < .05, **P < .01, ***P < .001, and ****P < .0001). In panels B-G and J, each black dot symbol represents 1 animal.