Experimental Surgical Research Laboratory, Department of General Surgery, Visceral, Thoracic and Vascular Surgery, Universitätsmedizin Greifswald, 17475 Greifswald, Germany.
Int J Mol Sci. 2021 Mar 27;22(7):3465. doi: 10.3390/ijms22073465.
Gram-negative infections of the peritoneal cavity result in profound modifications of peritoneal B cell populations and induce the migration of peritoneal B cells to distant secondary lymphoid organs. However, mechanisms controlling the egress of peritoneal B cells from the peritoneal cavity and their subsequent trafficking remain incompletely understood. Sphingosine-1-phosphate (S1P)-mediated signaling controls migratory processes in numerous immune cells. The present work investigates the role of S1P-mediated signaling in peritoneal B cell trafficking under inflammatory conditions.
Differential S1P receptor expression after peritoneal B cell activation was assessed semi‑quantitatively using RT-PCR in vitro. The functional implications of differential S1P and S1P expression were assessed by transwell migration in vitro, by adoptive peritoneal B cell transfer in a model of sterile lipopolysaccharide (LPS)‑induced peritonitis and in the polymicrobial colon ascendens stent peritonitis (CASP) model.
The two sphingosine-1-phosphate receptors (S1PRs) expressed in peritoneal B cell subsets S1P and S1P are differentially regulated upon stimulation with the TLR4 agonist LPS, but not upon PMA/ionomycin or B cell receptor (BCR) crosslinking. S1P deficiency affects both the trafficking of activated peritoneal B cells to secondary lymphoid organs and the positioning of these cells within the functional compartments of the targeted organ. S1P deficiency in LPS-activated peritoneal B cells results in significantly reduced numbers of splenic innate response activator B cells.
The S1P-S1PR system is implicated in the trafficking of LPS-activated peritoneal B cells. Given the protective role of peritoneal B1a B cells in peritoneal sepsis, further experiments to investigate the impact of S1P-mediated signaling on the severity and mortality of peritoneal sepsis are warranted.
革兰氏阴性菌引起的腹腔感染会导致腹腔 B 细胞群体发生深刻变化，并诱导腹腔 B 细胞迁移到远处的次级淋巴器官。然而，控制腹腔 B 细胞从腹腔逸出及其随后迁移的机制仍不完全清楚。鞘氨醇-1-磷酸（S1P）介导的信号转导控制着许多免疫细胞的迁移过程。本研究探讨了 S1P 介导的信号转导在炎症条件下对腹腔 B 细胞迁移的作用。
通过体外 RT-PCR 半定量评估腹腔 B 细胞激活后 S1P 受体的表达差异。通过体外 Transwell 迁移、无菌脂多糖（LPS）诱导腹膜炎模型中的腹腔 B 细胞过继转移以及多微生物结肠升支支架腹膜炎（CASP）模型来评估 S1P 和 S1P 表达的功能意义。
在 TLR4 激动剂 LPS 刺激下，两种表达于腹腔 B 细胞亚群 S1P 和 S1P 的鞘氨醇-1-磷酸受体（S1PR）的表达受到差异调节，但在 PMA/离子霉素或 B 细胞受体（BCR）交联时不受调节。S1P 缺乏会影响激活的腹腔 B 细胞向次级淋巴器官的迁移，以及这些细胞在靶向器官的功能区室中的定位。在 LPS 激活的腹腔 B 细胞中缺乏 S1P 会导致脾脏固有反应激活 B 细胞的数量显著减少。
S1P-S1PR 系统参与了 LPS 激活的腹腔 B 细胞的迁移。鉴于腹腔 B1a B 细胞在腹膜炎中的保护作用，进一步研究 S1P 介导的信号转导对腹膜炎严重程度和死亡率的影响是有必要的。
