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

Abstract

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 S1PR₁, S1PR₂ and S1PR₃ 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 S1PR₁ or S1PR₂. Different from BM neutrophils, the migration and cytoskeletal remodeling of dHL60 cells were mediated by S1PR₂ or S1PR₃. S1PR₂ 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.

Keywords: Liver Injury; Neutrophil; Recruitment; Sphingosine 1-phosphate receptors.