Critical role of stromal S1PR2 in the permeability and inflammatory phenotype of the endothelium during endotoxemia. (A) Reduced late-stage inflammation in S1pr2^+/+ → S1pr2^−/− chimeric mice (open bars) compared with S1pr2^+/+ → S1pr2^+/+ (solid bars) and with S1pr2^−/− → S1pr2^+/+ (shaded bars). Plasma IL-6 levels were measured 2 and 18 hours after LPS injection. Data are mean ± SEM (n = 4 to 7). (B) LPS-induced vascular permeability is inhibited in liver, lung, and heart of mice lacking S1PR2 in stromal cells (S1pr2^+/+ → S1pr2^−/−) compared with S1pr2^+/+ → S1pr2^+/+, but not in mice lacking S1PR2 in the hematopoietic compartment (S1pr2^−/− → S1pr2^+/+). Three hours after injection of LPS, vascular permeability was measured in liver, lungs, kidneys, spleen, heart, and brain by EBD extravasation assay. Values are mean ± SEM (n = 4 to 5). *P < .05 compared with S1pr2^+/+ → S1pr2^+/+. (C-E) Tissue mRNA levels of proinflammatory and procoagulant molecules in S1pr2^+/+ → S1pr2^+/+, S1pr2^+/+ → S1pr2^−/−, and S1pr2^−/− → S1pr2^+/+ mice 18 hours after LPS challenge. (C) Liver, (D) lung, (E) kidney. The results of quantitative real-time PCR analyses (mRNA copy number per 10⁶ copies of 18s rRNA) of E-selectin, VCAM-1, ICAM-1, TF, and MCP-1 are shown. Data are mean ± SEM (n = 6 to 7). *P < .05 compared with S1pr2^+/+ → S1pr2^+/+.