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.

过多的中性粒细胞会募集到受损的组织，并在慢性炎症条件下引起附带伤害。1-磷酸鞘氨醇（S1P）通过S1P受体（S1PRs）诱导各种细胞类型的募集，从而调节各种生理和病理作用。这项研究旨在检测慢性肝炎症过程中S1P / S1PRs介导的对嗜中性白细胞募集的影响。在本研究中，在BDL处理的小鼠的肝脏组织中检测到了源自骨髓（BM）的嗜中性粒细胞增多。肝鞘氨醇激酶1（SphK，S1P限速酶）或S1P水平与小鼠和患者肝脏中的中性粒细胞标志物表达呈正相关。体外S1PR ₁，S1PR ₂和S1PR _3的表达在小鼠的BM中性粒细胞和分化的人中性粒细胞样（dHL60）细胞中均检测到了TNF-α。S1P通过S1PR ₁或S1PR ₂强有力地促进了BM中性粒细胞的迁移和细胞骨架重塑。与BM中性粒细胞不同，dHL60细胞的迁移和细胞骨架重塑由S1PR ₂或S1PR ₃介导。S1PR ₂阻断明显减轻胆管结扎（BDL）引起的小鼠肝损伤中的中性粒细胞浸润。总之，S1P / S1PRs系统在中性粒细胞募集中起关键作用。