Figure 1. Endothelial-Specific Disruption of S1P Production Resulted in an Airspace-Enlargement Phenotype in Mice after PA Injury.

(A) Acute lung injury was induced by intratracheal (i.t.) injection of PA bacteria. BAL fluids were collected from uninjured and 72-h-post-injured lungs, S1P levels in the BAL were measured using LC-mass spectrometry.

(B) Lung alveoli are highly vascularized, with epithelial AT1 and AT2 cells residing closely to endothelial cells. To test the potential function of angiocrine S1P on AT2 cell progenitor function, we created VE-Cadherin-Cre/Sphk1^fl/fl mice (SphK1^ΔEC), in which Sphk1 expression was specifically disrupted in ECs.

(C) Sphk1 expression in ECs isolated from non-PA-treated WT and SphK1^ΔEC mice was analyzed by qPCR.

(D) S1P levels in BAL were measured in WT and SphK1^ΔEC mice at 72 h post-PA.

(E) Representative images of HE-stained lung sections of WT and SphK1^ΔEC mice without injury (non-PA) or 7 days after the last injection of three repetitive PA injuries at 1-week intervals (33 PA). Scale bar, 100 μm.

(F) Mean linear intercept (Lm) were measured from HE-stained lung sections.

Mean ± SEM. *p < 0.05. See also Figure S1