Fig. 4: HIF-1α mediates lactate release and inflammatory neutrophil mobilization.

a Gene expression of glycolytic enzymes in sorted BM neutrophils following LPS treatment (WT; n = 3, PBS; n = 5, LPS; HIF-1α^−/−, n = 3). On each box, the bottom, middle and the top edges indicate the 25th, 50th, and 75th percentiles, respectively. The whiskers extend to the most extreme data points. b Quantitative analysis and representative flow cytometry histogram plot of LDHA expression in BM neutrophils in WT (n = 6, PBS; n = 7, LPS) vs. HIF-1α^−/− (n = 6, PBS; n = 9, LPS) mice. c Quantitative analysis of MCT4 expression on BM neutrophils following either PBS or LPS treatment in WT (n = 6) vs. HIF-1α^−/− (n = 7, PBS; n = 6, LPS) mice.***p(WT + PBS vs. WT + LPS) = 0.0001; **p(WT + LPS vs. HIF-1α^−/−+LPS) = 0.0053. d BM lactate levels in WT (n = 5) vs. HIF-1α^−/− (n = 6) mice. **p(WT + PBS vs. WT + LPS) = 0.0023; **p(WT + LPS vs. HIF-1α^−/−+LPS) = 0.0020. e BM Lactate levels released from WT or HIF-1α^−/− isolated neutrophils treated in vitro with PBS or LPS (120 ng/ml; n = 4 each group) **p(WT + PBS vs. WT + LPS) = 0.0027. f PB neutrophils frequency in WT (n = 7) and HIF-1α^−/− (n = 7, PBS; n = 8, LPS) mice. g Liver neutrophil frequency in WT (n = 8) and HIF-1α^−/− (n = 8) mice following LPS treatment. h PB neutrophil frequency in WT (n = 5, PBS; n = 6, lactate) and HIF-1α^−/− (n = 5) mice following 50.5 mg lactate treatment. i Liver neutrophil frequency in WT vs. HIF-1α^−/− (n = 4, PBS; n = 3, lactate) following lactate administration. Data are represented as mean ± SEM from 3 to 4 independent experiments. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001, two-way ANOVA with Bonferroni post hoc test (a) or two-way ANOVA with Tukey’s post hoc test (b–i). See also Supplementary Fig. 5.