Fig. 8.
Pharmacologic inhibition of S1PR2 increases bacterial phagocytosis of macrophages and improved survival of wild-type (WT, S1pr2+/+) mice challenged with a lethal dose of Escherichia coli. (A) Inhibition of S1PR2 enhances phagocytosis of WT bone marrow–derived macrophages (BMDMs). WT and S1pr2−/− BMDMs were starved and pretreated with 5 μM JTE-013 (an S1PR2 antagonist) or vehicle for 30 min before stimulation with 100 nM S1P for another 30 min. Phagocytosis was assessed as described in fig. 3B. Data were analyzed by two-way ANOVA with Bonferroni corrections. (B) JTE-013 treatment protects WT mice from lethal infection caused by E. coli infection. WT mice were intratracheally instilled with JTE-013 (4 mg/kg) or vehicle 30 min before E. coli infection. The survival rates were assessed. n = 11 for the vehicle control group, and n = 9 for JTE-013 group from two independent experiments. Data were analyzed by Mantel–Cox test. (C, D) Number of E. coli bacteria recovered from blood (C) and lung tissue (D) from the JTE-013 treatment group or control group at 4 h after bacterial infection. n = 5 at each time point. Data are presented as mean ± SD and were analyzed by Student t test. BALF = bronchoalveolar lavage fluid. S1PR2 = sphingosine 1-phosphate receptor 2. *P < 0.05, **P < 0.01, and ***P < 0.001.

Pharmacologic inhibition of S1PR2 increases bacterial phagocytosis of macrophages and improved survival of wild-type (WT, S1pr2+/+) mice challenged with a lethal dose of Escherichia coli. (A) Inhibition of S1PR2 enhances phagocytosis of WT bone marrow–derived macrophages (BMDMs). WT and S1pr2−/− BMDMs were starved and pretreated with 5 μM JTE-013 (an S1PR2 antagonist) or vehicle for 30 min before stimulation with 100 nM S1P for another 30 min. Phagocytosis was assessed as described in fig. 3B. Data were analyzed by two-way ANOVA with Bonferroni corrections. (B) JTE-013 treatment protects WT mice from lethal infection caused by E. coli infection. WT mice were intratracheally instilled with JTE-013 (4 mg/kg) or vehicle 30 min before E. coli infection. The survival rates were assessed. n = 11 for the vehicle control group, and n = 9 for JTE-013 group from two independent experiments. Data were analyzed by Mantel–Cox test. (C, D) Number of E. coli bacteria recovered from blood (C) and lung tissue (D) from the JTE-013 treatment group or control group at 4 h after bacterial infection. n = 5 at each time point. Data are presented as mean ± SD and were analyzed by Student t test. BALF = bronchoalveolar lavage fluid. S1PR2 = sphingosine 1-phosphate receptor 2. *P < 0.05, **P < 0.01, and ***P < 0.001.

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