Sphingosylphosphorylcholine 抑制巨噬细胞与血管平滑肌细胞的粘附。,BIOCHEMICAL PHARMACOLOGY

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Sphingosylphosphorylcholine 抑制巨噬细胞与血管平滑肌细胞的粘附。
BIOCHEMICAL PHARMACOLOGY ( IF 5.3 ) Pub Date : 2016 Jul 8 , DOI: 10.1016/j.bcp.2016.07.004
Christiane Wirrig ₁ , Jenny S McKean ₁ , Heather M Wilson ₁ , Graeme F Nixon ₁

Affiliation

去内皮化动脉中的炎症有助于心血管疾病的发展。引发这种炎症反应的过程是单核细胞/巨噬细胞与暴露的血管平滑肌细胞的粘附，通常由细胞因子如肿瘤坏死因子-α (TNF) 刺激。本研究的目的是确定鞘脂类鞘氨醇磷酸胆碱 (SPC) 对单核细胞/巨噬细胞与血管平滑肌细胞相互作用的影响。大鼠主动脉平滑肌细胞和大鼠骨髓来源的巨噬细胞在与鞘脂孵育后使用体外试验共培养以评估细胞间粘附。我们揭示 SPC 抑制 TNF 诱导的巨噬细胞与平滑肌细胞的粘附。这种抗粘附作用是 SPC 诱导的平滑肌细胞（但不是巨噬细胞）变化的结果，并且至少部分是通过 1-磷酸鞘氨醇受体亚型 2 介导的。还需要脂筏结构域。尽管 SPC 没有改变平滑肌细胞中粘附蛋白细胞间粘附分子 1 和血管细胞粘附蛋白 1 的表达或膜分布，但 SPC 预孵育抑制了 TNF 诱导的诱导型一氧化氮合酶 (NOS2) 的增加，导致随后的一氧化氮的产生减少。抑制平滑肌细胞中的 NOS2 活化导致巨噬细胞与平滑肌细胞的粘附减少。因此，本研究描绘了一种新的途径，该途径可以通过 SPC 诱导的 NOS2 表达抑制来抑制巨噬细胞和血管平滑肌细胞之间的相互作用。这种机制可能代表血管疾病的潜在药物靶点。

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Sphingosylphosphorylcholine inhibits macrophage adhesion to vascular smooth muscle cells.

Inflammation in de-endothelialized arteries contributes to the development of cardiovascular diseases. The process that initiates this inflammatory response is the adhesion of monocytes/macrophages to exposed vascular smooth muscle cells, typically stimulated by cytokines such as tumour necrosis factor-alpha (TNF). The aim of this study was to determine the effect of the sphingolipid sphingosylphosphorylcholine (SPC) on the interaction of monocytes/macrophages with vascular smooth muscle cells. Rat aortic smooth muscle cells and rat bone marrow-derived macrophages were co-cultured using an in vitro assay following incubation with sphingolipids to assess inter-cellular adhesion. We reveal that SPC inhibits the TNF-induced adhesion of macrophages to smooth muscle cells. This anti-adhesive effect was the result of SPC-induced changes to the smooth muscle cells (but not the macrophages) and was mediated, at least partly, via the sphingosine 1-phosphate receptor subtype 2. Lipid raft domains were also required. Although SPC did not alter expression or membrane distribution of the adhesion proteins intercellular adhesion molecule-1 and vascular cellular adhesion protein-1 in smooth muscle cells, SPC preincubation inhibited the TNF-induced increase in inducible nitric oxide synthase (NOS2) resulting in a subsequent decrease in nitric oxide production. Inhibiting NOS2 activation in smooth muscle cells led to a decrease in the adhesion of macrophages to smooth muscle cells. This study has therefore delineated a novel pathway which can inhibit the interaction between macrophages and vascular smooth muscle cells via SPC-induced repression of NOS2 expression. This mechanism could represent a potential drug target in vascular disease.

更新日期：2017-01-31

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