RvD4 regulates neutrophil infiltration in a dose-dependent manner. (A-C) Mice inoculated with E coli (105 CFU, IP) were also (IV) administered RvD4 (100 ng per mouse) or vehicle alone (0.01% v/v ethanol in saline). Exudates, whole blood, and BM cells were collected at 12 hours. Levels of G-CSF, CXCL1, and CXCL12 in the serum, BM, and exudate. Results are expressed as mean ± SEM; n = 3 to 5 samples per condition. RvD4 vs E coli + vehicle, ∗P < .05, ∗∗P < .01, ∗∗∗P < .001 using 2-tailed t test. (D) LTB4 whole-blood neutrophil mobilization. Naïve mice were IV administered LTB4 (red line), RvD4 (dark blue line), combination of RvD4 + LTB4 (purple), or vehicle only (0.01% ethanol v/v in saline). Neutrophils were enumerated by light microscopy and differential count. Results are expressed as mean ± SEM; n = 6 mice per condition. Time 0 minute vs 5, 10, 15, 20, 30, 40, and 60 minutes, respectively; ∗P < .05, ∗∗∗ P < .001, ∗∗∗∗P < .0001. RvD4 + LTB4 vs LTB4; ###P < .001, using 2-way ANOVA with Bonferroni multiple comparisons test. (E-G) Mice were inoculated with E coli (105 CFU, IP) and administered (IV) RvD4 at concentrations of 1, 10, or 100 ng per mouse, or vehicle only (0.01% v/v ethanol in saline). Exudates and whole blood were collected at 12 hours. (E) Cell number of neutrophils (CD45+F4/80−Ly6C−Ly6G+) in peritoneal exudates; (F) levels of CXCL1 in exudate; (G) levels of G-CSF and CXCL12 in the serum. (E-G) Results are expressed as mean ± SEM; n = 7 (RvD4, 1 ng per mouse), n = 8 (RvD4, 10 ng per mouse), n = 4 (RvD4, 100 ng per mouse), or n = 9 (E coli + vehicle). RvD4 vs E coli + vehicle; ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, ∗∗∗∗P < .0001 with 2-way ANOVA with Bonferroni multiple comparisons test.