Carulli G, Minnucci S, Gianfaldoni M L, Angiolini C, Azzarà A, Ambrogi F
Unit of Hematology, University of Pisa, Italy.
Eur J Clin Invest. 1995 Dec;25(12):929-34. doi: 10.1111/j.1365-2362.1995.tb01969.x.
Essential thrombocythaemia (ET) is frequently associated with neutrophil and platelet dysfunction, and with increased incidence of vascular complications (thrombosis, haemorrhage). Several interactions between platelets and neutrophils have been reported, and the reciprocal actions between these cells may have an important role both in thromboregulation and in diseases such as those caused by uncontrolled neutrophil activation. In the current paper the authors studied 15 patients affected by ET and 10 normal subjects as controls. Circulating neutrophils and platelets were purified and were recombined in constant ratios (50:1, 100:1 and 200:1) and the individual platelet to neutrophil ratio. Superoxide anion (O2-) generation and luminol-enhanced chemiluminescence (CL) were studied after neutrophil stimulation with fMLP. In normal subjects both O2- generation and CL were inhibited by autologous platelets in a dose-dependent manner. In ET patients, on the contrary, platelet-dependent inhibition of O2- generation did not occur, while a dose-dependent inhibition of CL was observed. Two groups of ET patients were found: patients with neutrophil O2- generation and CL within the normal range, and patients with significantly reduced neutrophil respiratory burst. However, no differences were found between these two groups of patients in terms of platelet effects towards fMLP-stimulated neutrophils. Therefore, platelets from ET patients were not able to exert the homeostatic control towards neutrophil O2- generation shown by platelets from normal subjects, and this phenomenon may have a role in the clinical setting. In fact, O2- has been shown to be a very strong direct platelet activator, is able to inactivate nitric oxide (which is a powerful inhibitor of platelet aggregation and adhesion to endothelium), and is directly involved in neutrophil-mediated tissue damage.
原发性血小板增多症（ET）常与中性粒细胞和血小板功能障碍相关，且血管并发症（血栓形成、出血）的发生率增加。已有多项关于血小板与中性粒细胞之间相互作用的报道，这些细胞之间的相互作用可能在血栓调节以及由中性粒细胞不受控制的激活所引起的疾病中发挥重要作用。在本论文中，作者研究了15例ET患者及10名正常受试者作为对照。将循环中的中性粒细胞和血小板纯化，并以恒定比例（50:1、100:1和200:1）以及个体血小板与中性粒细胞的比例进行重组。在用fMLP刺激中性粒细胞后，研究超氧阴离子（O2-）的生成和鲁米诺增强化学发光（CL）。在正常受试者中，自体血小板以剂量依赖性方式抑制O2-的生成和CL。相反，在ET患者中，未发生血小板依赖性的O2-生成抑制，而观察到CL的剂量依赖性抑制。发现ET患者分为两组：中性粒细胞O2-生成和CL在正常范围内的患者，以及中性粒细胞呼吸爆发明显降低的患者。然而，在这两组患者中，血小板对fMLP刺激的中性粒细胞的作用方面未发现差异。因此，ET患者的血小板无法对中性粒细胞O2-生成发挥正常受试者血小板所表现出的稳态控制作用，这种现象可能在临床环境中起作用。事实上，O2-已被证明是一种非常强的直接血小板激活剂，能够使一氧化氮（一种强大的血小板聚集和黏附于内皮的抑制剂）失活，并且直接参与中性粒细胞介导的组织损伤。
