Akopov S E, Sercombe R, Seylaz J
Laboratoire de Recherches Cérébrovasculaires, CNRS UA 641, Université Paris VII, France.
J Lipid Mediat Cell Signal. 1995 May;11(3):267-79. doi: 10.1016/0929-7855(94)00044-d.
We studied the effects of polymorphonuclear leukocytes (PMNLs) activated by N-formyl-methionyl-leucyl-phenylalanine on the endothelium-dependent relaxation of the rabbit basilar artery (BA). In the presence of activated PMNLs the maximal vessel relaxation to acetylcholine (ACh) and bradykinin (endothelium-dependent dilators) was decreased from 62 +/- 7 and 48 +/- 6% to 23 +/- 9 and 19 +/- 7, respectively, (p < 0.05). The endothelium-independent relaxation to nitroprusside was not affected by PMNLs. When PMNLs were activated in the organ chamber in the presence of a low concentration of platelet-activating factor (PAF, 10(-10) mol/l), the depression of ACh- and bradykinin-induced relaxation increased by 27 +/- 9 and 23 +/- 7%, respectively (p < 0.05), though at this concentration PAF alone did not cause PMNLs to induce endothelial dysfunction. In addition, in the presence of PAF, activated PMNLs inhibited endothelium-dependent relaxation at lower cell concentrations and shorter periods of contact with the endothelium. PMNL effects on the endothelium were correlated with the level of cell exocytosis as tested by accumulation of beta-glucuronidase activity. In the presence of PAF, accumulation of this activity increased from 46 +/- 6 to 79 +/- 8 U/ml (p < 0.05). Examination of BA segments by scanning electron microscopy revealed that, after the treatment with activated PMNLs, the endothelium was morphologically preserved, but in the presence of PAF PMNLs caused more apparent microlesions in the endothelial layer. We conclude that small quantities of PAF potentiate the activation of marginated PMNLs. These cells then become more aggressive towards the endothelium, producing significant depression of the endothelium-dependent relaxation.
我们研究了由N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸激活的多形核白细胞（PMNLs）对兔基底动脉（BA）内皮依赖性舒张的影响。在存在活化的PMNLs的情况下，血管对乙酰胆碱（ACh）和缓激肽（内皮依赖性舒张剂）的最大舒张分别从62±7%和48±6%降至23±9%和19±7%（p<0.05）。对硝普钠的非内皮依赖性舒张不受PMNLs影响。当在低浓度血小板活化因子（PAF，10⁻¹⁰mol/L）存在下在器官腔中激活PMNLs时，ACh和缓激肽诱导的舒张抑制分别增加27±9%和23±7%（p<0.05），尽管在此浓度下单独的PAF不会导致PMNLs诱导内皮功能障碍。此外，在PAF存在下，活化的PMNLs在较低细胞浓度和与内皮较短接触时间时抑制内皮依赖性舒张。通过β-葡萄糖醛酸酶活性积累测试，PMNLs对内皮的作用与细胞胞吐水平相关。在PAF存在下，该活性积累从46±6 U/ml增加到79±8 U/ml（p<0.05）。通过扫描电子显微镜检查BA段发现，用活化的PMNLs处理后，内皮在形态上得以保留，但在PAF存在下，PMNLs在内皮层中引起更明显的微损伤。我们得出结论，少量的PAF增强了边缘PMNLs的活化。这些细胞随后对内皮变得更具侵袭性，导致内皮依赖性舒张显著降低。
