S1pr2 null mice display decreased inflammation during endotoxemia. (A) Reduced late-stage inflammation in S1pr2^−/− mice (knockout [KO]) compared with WT mice documented by plasma IL-6 levels at various time points following LPS administration. Data are mean ± standard error of the mean (SEM) (n = 4 to 14). (B) LPS-induced vascular permeability is abrogated in mice lacking S1PR2. Six hours after injection of vehicle (–) or LPS (+), vascular permeability was measured in liver, lungs, kidneys, spleen, heart, and brain by the Evans blue dye extravasation (EBD) assay. Values are mean ± SEM (n = 4). *P < .05 compared with the respective untreated controls and, where indicated, between WT and S1pr2^−/− mice. (C-E) Tissue mRNA expression levels of proinflammatory and procoagulant molecules in S1pr2^+/+ (WT) and S1pr2^−/− (KO) mice 18 hours after vehicle (C) or LPS challenge. (C) Liver, (D) lung, (E) kidney. The results of quantitative real-time polymerase chain reaction (PCR) analyses (mRNA copy number per 10⁶ copies of 18s ribosomal RNA [rRNA]) of E-selectin, VCAM-1, ICAM-1, TF, and MCP-1 are shown. Data are mean ± SEM (n = 4 to 5) of one representative experiment of three with similar results. *P < .05 compared with the respective untreated controls (C vs LPS) and, where indicated, between WT and S1pr2^−/− mice.