S1PR2-deficient alveolar macrophages (AMs) show enhanced phagocytic function. (A) Representative microscopic images of red fluorescent–labeled Escherichia coli engulfed by isolated wild-type (WT, S1pr2^+/+) and S1pr2^−/− AMs. The bacteria were also pretreated with or without opsonin. Magnification is ×200. (B) Quantification of phagocytosis according to fluorescent microscopic images in A. In each microscopic field, total AMs and fluorescent intensity (FI) inside these cells were quantified. The average FI per AM was calculated as total FI per field/total number of AMs per field. Three fields per sample were analyzed. n = 4 for WT AMs groups, and n = 6 for S1pr2^−/− AMs groups. Data are presented as mean ± SD and were analyzed by two-way ANOVA with Bonferroni corrections. (C, D) Killing curves of internalized E. coli in WT and S1pr2^−/− AMs. n = 4 per group. Data are presented as mean ± SD and were analyzed by Mann–Whitney test. (E) Survival curve in S1pr2^−/− and WT mice with opsonized E. coli (2 × 10⁶ colony forming units [CFU]) induced lung injury. Data consist of two independent experiments (n = 13 or WT group, n = 14 for S1pr2^−/− group) and were analyzed by Mantel-Cox test. S1PR2 = sphingosine 1-phosphate receptor 2. **P < 0.01 and ***P < 0.001.