Boguslawski George, Grogg Jeremy R, Welch Zachary, Ciechanowicz Sandra, Sliva Daniel, Kovala A Thomas, McGlynn Patrick, Brindley David N, Rhoades Rodney A, English Denis
Experimental Cell Research Laboratory, Methodist Research Institute, Indianapolis, Indiana 46202, USA.
Exp Cell Res. 2002 Apr 1;274(2):264-74. doi: 10.1006/excr.2002.5472.
The bioactive lipids sphingosine 1-phosphate (SPP), sphingosylphosphorylcholine, and lysophosphatidic acid play an important role in angiogenesis as a result of their effects on both the migration of endothelial cells (ECs) and the integrity of EC monolayers. Here we show that extremely low concentrations of serum and nanomolar concentrations of these biologically active lipids stimulate migration of human aortic smooth muscle cells (SMCs). However, at dosages most effective in promoting EC migration and in enhancing EC monolayer integrity, serum and SPP potently inhibited SMC migration; SPP also blocked the migration induced by protein growth factors. Treatment of SMCs with SPP induced transient phosphorylation of a 175- to 185-kDa protein corresponding to the PDGF receptor, indicating transactivation of this receptor. SPP and related lipids may play a key role in angiogenesis by coordinating the migration of both endothelial cells and vascular smooth muscle cells in response to the changing gradients of these bioactive lipid messengers.
生物活性脂质鞘氨醇-1-磷酸（SPP）、鞘氨醇磷酰胆碱和溶血磷脂酸因其对内皮细胞（ECs）迁移和EC单层完整性的影响，在血管生成中发挥重要作用。在此我们表明，极低浓度的血清和纳摩尔浓度的这些生物活性脂质可刺激人主动脉平滑肌细胞（SMCs）迁移。然而，在促进EC迁移和增强EC单层完整性方面最有效的剂量下，血清和SPP可有效抑制SMC迁移；SPP还可阻断蛋白质生长因子诱导的迁移。用SPP处理SMC会诱导与血小板衍生生长因子（PDGF）受体相对应的175至185 kDa蛋白发生瞬时磷酸化，表明该受体发生反式激活。SPP及相关脂质可能通过响应这些生物活性脂质信使的变化梯度协调内皮细胞和血管平滑肌细胞的迁移，在血管生成中发挥关键作用。
