Kang Shijun, Yang Chunlan, Luo Rongcheng
Department of Oncology, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China.
Lipids. 2008 Nov;43(11):1075-83. doi: 10.1007/s11745-008-3238-6. Epub 2008 Oct 2.
As a transmembrane chemokine, CXCL16 has been detected in various tissues and organs under normal and pathological conditions, it also plays an important role in macrophages/dendritic cells (DC) and T cell interactions and trafficking during inflammation and immune responses. LysoPtdOH, a bioactive lipid mediator has been indicated to regulate DC and epithelial functions during wound healing and inflammation responses. However, the direct link of CXCL16 expression with lysoPtdOH has not been established. Using monocyte-derived macrophages/DC (MoDC), we investigated the roles of lysoPtdOH in CXCL16 production and cell surface presentation. We found that macrophages/MoDC constitutively express and secrete CXCL16, lysoPtdOH significantly enhanced CXCL16 protein production stimulated with lipopolysaccharide (LPS) by more than twofold, which was reflected by increased mRNA transcription by 64-fold. Production of CXCL16 increased by lysoPtdOH and LPS from macrophages was inhibited around 70% by Pertussis toxin (G(i/o) specific inhibitor), exoC3 (Rho specific inhibitor), and pyrrolidine dithiocarbamate (the NF-kappaB-dependent pathway inhibitor) separately. LysoPtdOH treatment increased macrophages' chemotactic activity to activated T cells. The soluble form of CXCL16 produced by macrophages/MoDC was functionally chemoattractive to T cells.
作为一种跨膜趋化因子，CXCL16在正常和病理条件下的各种组织和器官中均有检测到，它在炎症和免疫反应过程中的巨噬细胞/树突状细胞（DC）与T细胞相互作用及迁移中也发挥着重要作用。溶血磷脂酸（LysoPtdOH）是一种生物活性脂质介质，已被证明在伤口愈合和炎症反应过程中调节DC和上皮细胞功能。然而，CXCL16表达与LysoPtdOH之间的直接联系尚未确立。我们使用单核细胞衍生的巨噬细胞/DC（MoDC），研究了LysoPtdOH在CXCL16产生和细胞表面呈递中的作用。我们发现巨噬细胞/MoDC组成性表达并分泌CXCL16，LysoPtdOH显著增强脂多糖（LPS）刺激的CXCL16蛋白产生，增幅超过两倍，这反映在mRNA转录增加64倍。来自巨噬细胞的LysoPtdOH和LPS所增加的CXCL16产生分别被百日咳毒素（G(i/o)特异性抑制剂）、外切C3（Rho特异性抑制剂）和吡咯烷二硫代氨基甲酸盐（NF-κB依赖途径抑制剂）抑制约70%。LysoPtdOH处理增加了巨噬细胞对活化T细胞的趋化活性。巨噬细胞/MoDC产生的可溶性CXCL16形式对T细胞具有功能上的趋化作用。
