Fig. 6: GPR81/lactate signaling mediates neutrophil mobilization.

a, b Frequency of neutrophils in the BM (a, n = 9) and quantitative analysis and representative flow cytometry density plots for PB neutrophils (b, n = 8) following lactate treatment in WT vs. GPR81^−/− mice. **p(GPR81^−/− + PBS vs. GPR81^−/− + lactate) =0.0017. c Frequency of BM neutrophils in WT (n = 9, PBS; n = 8, LPS) vs. GPR81^−/− (n = 9, PBS; n = 8, LPS) mice following LPS treatment. d Frequency of PB neutrophils following LPS administration (n = 7). e Quantitative analysis and representative flow cytometry density plots for PB neutrophils following blocking VE–cadherin antibodies in GPR81^−/− mice (n = 4). *p(LPS vs. αVE–Cad + LPS) = 0.0402. f Levels of BM EBD absorbance following lactate treatment in chimeric mice (n = 5, WT to WT + PBS; n = 4, WT to WT + lactate; n = 4, GPR81^−/− to WT; n = 4, WT to GPR81^−/−). g, h Neutrophil frequency in the PB (g, n = 4, WT to WT; n = 3, GPR81^−/− to WT; n = 5, WT to GPR81^−/−), and in the liver of chimeric mice (h, n = 4, WT to WT; n = 3, GPR81^−/− to WT; n = 5, WT to GPR81^−/−) following lactate administration. i, j Frequency of neutrophils in the BM (i; n = 5, PBS; n = 6, lactate) and blood (j, n = 6) following lactate treatment in GPR81^f/f/Cdh5^{cre neg} vs. GPR81^f/f/Cdh5^{cre pos} mice. k, l Plasma protein levels of CXCL1 in k WT vs. GPR81^−/− mice (WT; n = 9, PBS; n = 8, lactate; GPR81^−/−; n = 8) or l GPR81^f/f/Cdh5^{cre neg} vs. GPR81^f/f/Cdh5^{cre pos} mice (n = 6, PBS; n = 7, lactate; per mice group) following lactate treatment. m Plasma protein levels of G-CSF in WT vs. GPR81^−/− mice (n = 6, WT + PBS, WT + lactate and GPR81^−/− + lactate; n = 5 GPR81^−/− + PBS) following lactate treatment. Data are represented as mean ± SEM from 3 to 5 independent experiments. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001, two-way ANOVA with Tukey’s post hoc test (a–d, f–m) or one-way ANOVA with Tukey’s post hoc test (e). See also Supplementary Fig. 7.