Lysoplasmenylcholine increases neutrophil adherence to human coronary artery endothelial cells.
Lysoplasmenylcholine increases neutrophil adherence to human coronary artery endothelial cells.
复制标题
溶浆胆碱增加中性粒细胞对人冠状动脉内皮细胞的粘附。
DOI：
10.1152/ajpcell.00290.2007
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
McHowat,Jane
中科院分区：
文献类型：
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作者：
White,MaureenC;Rastogi,Prerna;McHowat,Jane
我们先前证明，凝血酶刺激人冠状动脉内皮细胞（HCAEC）导致释放胆碱溶血磷脂[溶血磷脂酰胆碱（lysoPtdCho）和溶血胞浆胆碱（lysoPlsCho）]。这些两亲性代谢物与心肌缺血发作后的血管生成有关，但研究其对血管系统的直接影响仍然有限。我们和其他人已经表明凝血酶和lysoPtdCho可以增加细胞表面粘附分子和循环炎性细胞对内皮的粘附。这项研究支持了我们的假设，即这些变化可能至少部分由lysoPlsCho介导，从而暗示这种代谢物是冠状血管中的炎症介质和动脉粥样硬化进展的调节剂。用凝血酶刺激HCAEC的顶端导致从HCAEC单层的顶端表面产生和释放胆碱溶血磷脂。基底外侧刺激对胆碱溶血磷脂的产生或从HCAEC单层的顶端或基底外侧表面释放没有影响。HCAEC与lysoPlsCho或lysoPtdCho的孵育导致HCAEC表面P-选择素和E-选择素表达的类似增加。此外，lysoPlsCho增加细胞表面的P-选择素，E-选择素，血管细胞粘附分子-1，1和细胞间粘附分子-1的表达与凝血酶刺激的时间过程相似。细胞表面粘附分子的存在增加可能有助于嗜中性粒细胞对凝血酶或lysoPlsCho刺激的HCAEC的粘附的显著增加。这些结果表明，在冠状动脉循环中血管损伤部位存在凝血酶，导致HCAEC顶端表面释放的胆碱溶血磷脂增加，有可能通过上调粘附分子和募集循环炎性细胞至内皮来传播血管炎症。
We demonstrated previously that thrombin stimulation of human coronary artery endothelial cells (HCAEC) results in release of choline lysophospholipids [lysophosphatidylcholine (lysoPtdCho) and lysoplasmenylcholine (lysoPlsCho)]. These amphiphilic metabolites have been implicated in arrhythmogenesis following the onset of myocardial ischemia, but studies examining their direct effects on the vasculature remain limited. We and others have shown that thrombin and lysoPtdCho can increase cell surface adhesion molecules and adherence of circulating inflammatory cells to the endothelium. This study supports our hypothesis that these changes may be mediated, at least in part, by lysoPlsCho, thus implicating this metabolite as an inflammatory mediator in the coronary vasculature and a modulator of the progression of atherosclerosis. Apical stimulation of HCAEC with thrombin resulted in the production and release of choline lysophospholipids from the apical surface of the HCAEC monolayer. Basolateral stimulation had no effect on choline lysophospholipid production or release from either the apical or basolateral surface of the HCAEC monolayer. Incubation of HCAEC with lysoPlsCho or lysoPtdCho resulted in similar increases in HCAEC surface expression of P-selectin and E-selectin. Furthermore, lysoPlsCho increased cell surface expression of P-selectin, E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 with a time course similar to that of thrombin stimulation. Increased presence of cell surface adhesion molecules may contribute to the significant increase in adherence of neutrophils to either thrombin- or lysoPlsCho-stimulated HCAEC. These results demonstrate that the presence of thrombin at sites of vascular injury in the coronary circulation, resulting in increased choline lysophospholipid release from the HCAEC apical surface, has the potential to propagate vascular inflammation by upregulation of adhesion molecules and recruitment of circulating inflammatory cells to the endothelium.