Neutrophil recruitment mediated by sphingosine 1-phosphate (S1P)/S1P receptors during chronic liver injury

Excessive neutrophils are recruited to damaged tissue and cause collateral injury under chronic inflammatory conditions. Sphingosine 1-phosphate (S1P) modulates kinds of physiological and pathological actions by inducing recruitment of various cell types through S1P receptors (S1PRs). This study aimed to detect the S1P/S1PRs-mediated effects on neutrophil recruitment during chronic liver inflammation. In present study, increased neutrophils originated from bone marrow (BM) were detected in liver tissue of BDL-treated mice. Hepatic sphingosine kinase 1 (SphK, S1P rate-limiting enzyme) or S1P levels positively correlated with neutrophil marker expression in liver of mice and patients. In vitro, expression of S1PR(1), S1PR(2) and S1PR(3) were detected in both mouse BM neutrophils and differentiated human neutrophil-like (dHL60) cells. S1P powerfully boosted the migration and cytoskeletal remodeling of BM neutrophils through S1PR(1) or S1PR(2). Different from BM neutrophils, the migration and cytoskeletal remodeling of dHL60 cells were mediated by S1PR(2) or S1PR(3). S1PR(2) blockade obviously attenuates neutrophil infiltration in bile duct ligation (BDL)-induced mouse liver injury. In conclusion, S1P/S1PRs system plays a pivotal role in neutrophil recruitment.

Automated summary

This study identified that in chronic liver inflammation, the S1P/S1PRs system plays a crucial role in the recruitment of neutrophils. S1P enhances the migration and cytoskeletal remodeling of bone marrow (BM) neutrophils through S1PR(1) and S1PR(2), while the migration and cytoskeletal remodeling of dHL60 cells are mainly mediated by S1PR(2) and S1PR(3). Blocking S1PR(2) significantly reduces neutrophil infiltration in bile duct ligation (BDL)-induced mouse liver injury.