Fig. 3: Lactate production by neutrophils requires NOX/ROS signaling.

a Percentage of BM HIF-1α+ neutrophils in WT (n = 9) and gp91phox−/− (n = 7) mice treated with either PBS or LPS. **p(WT + LPS vs. gp91phox−/−+LPS) = 0.0012. b Quantitative analysis and representative histogram plot showing LDHA expression in BM neutrophils from WT (n = 5) and gp91phox−/− (n = 4) mice. **p(WT + PBS vs. WT + LPS) = 0.0054; *p(WT + LPS vs. gp91phox−/−+LPS) = 0.0131. c Quantitative analysis of MCT4 expression on BM neutrophils from WT (n = 7) and gp91phox−/− (n = 7) mice treated with either PBS or LPS. *p(gp91phox−/−+PBS vs. gp91phox−/−+LPS) = 0.0424. d BM lactate levels in WT (n = 4, PBS; n = 5, LPS) and gp91phox−/− (n = 5, PBS; n = 6, LPS) mice treated with LPS. e BM lactate levels released from WT or gp91phox−/− isolated neutrophils treated ex vivo with PBS or LPS (120 ng/ml; n = 4, WT; n = 3, gp91phox−/−). f, g Frequency of PB neutrophils from WT and gp91phox−/− (f, n = 6; **p(WT + PBS vs. WT + LPS) = 0.0058) and ROShigh neutrophils (g, n = 7, WT + PBS; n = 6, WT + LPS; n = 6, gp91phox−/− mice) following LPS injection. h Quantitative analysis and representative histogram plot of PB ROShigh neutrophils of gp91phox−/− mice treated with PBS, LPS, or LPS together with 50.5 mg lactate (n = 8, PBS or LPS; n = 6, LPS + lactate).**p(LPS vs. LPS + lactate) = 0.0018. Data are represented as mean ± SEM from 3 to 4 independent experiments. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001, one-way ANOVA with Tukey’s post hoc test (h) or two-way ANOVA with Tukey’s post hoc test (a–g). See also Supplementary Fig. 4.