Università Vita-Salute San Raffaele and San Raffaele Scientific Institute, Milano, Italy.
PLoS One. 2012;7(6):e39484. doi: 10.1371/journal.pone.0039484. Epub 2012 Jun 25.
Neutrophils are involved in thrombus formation. We investigated whether specific features of neutrophil activation characterize patients with acute coronary syndromes (ACS) compared to stable angina and to systemic inflammatory diseases.
The myeloperoxidase (MPO) content of circulating neutrophils was determined by flow cytometry in 330 subjects: 69 consecutive patients with acute coronary syndromes (ACS), 69 with chronic stable angina (CSA), 50 with inflammation due to either non-infectious (acute bone fracture), infectious (sepsis) or autoimmune diseases (small and large vessel systemic vasculitis, rheumatoid arthritis). Four patients have also been studied before and after sterile acute injury of the myocardium (septal alcoholization). One hundred thirty-eight healthy donors were studied in parallel. Neutrophils with normal MPO content were 96% in controls, >92% in patients undergoing septal alcoholization, 91% in CSA patients, but only 35 and 30% in unstable angina and AMI (STEMI and NSTEMI) patients, compared to 80%, 75% and 2% of patients with giant cell arteritis, acute bone fracture and severe sepsis. In addition, in 32/33 STEMI and 9/21 NSTEMI patients respectively, 20% and 12% of neutrophils had complete MPO depletion during the first 4 hours after the onset of symptoms, a feature not observed in any other group of patients. MPO depletion was associated with platelet activation, indicated by P-selectin expression, activation and transactivation of leukocyte β2-integrins and formation of platelet neutrophil and -monocyte aggregates. The injection of activated platelets in mice produced transient, P-selectin dependent, complete MPO depletion in about 50% of neutrophils.
ACS are characterized by intense neutrophil activation, like other systemic inflammatory syndromes. In the very early phase of acute myocardial infarction only a subpopulation of neutrophils is massively activated, possibly via platelet-P selectin interactions. This paroxysmal activation could contribute to occlusive thrombosis.
中性粒细胞参与血栓形成。我们研究了与稳定型心绞痛和全身性炎症性疾病相比，中性粒细胞激活的特定特征是否能表征急性冠脉综合征（ACS）患者。
通过流式细胞术测定了 330 例患者（69 例连续的急性冠脉综合征（ACS）患者，69 例慢性稳定型心绞痛（CSA）患者，50 例非感染性（急性骨折）、感染性（败血症）或自身免疫性疾病（小和大血管全身性血管炎、类风湿关节炎）引起炎症的患者）循环中性粒细胞的髓过氧化物酶（MPO）含量。还研究了 4 例无菌性急性心肌损伤（间隔酒精化）前后的患者。同时研究了 138 例健康供体。对照组中 MPO 含量正常的中性粒细胞占 96%，间隔酒精化的患者占 92%，CSA 患者占 91%，但不稳定型心绞痛和 AMI（STEMI 和 NSTEMI）患者仅占 35%和 30%，而巨细胞动脉炎、急性骨折和严重败血症患者分别占 80%、75%和 2%。此外，在 32/33 例 STEMI 和 9/21 例 NSTEMI 患者中，分别有 20%和 12%的中性粒细胞在症状发作后的头 4 小时内出现完全 MPO 耗竭，这一特征在其他患者群体中均未观察到。MPO 耗竭与血小板激活有关，表现为 P-选择素表达、白细胞β2-整合素激活和转激活以及血小板-中性粒细胞和 -单核细胞聚集体形成。在小鼠中注射激活的血小板可导致约 50%的中性粒细胞发生短暂的、依赖于 P-选择素的、完全的 MPO 耗竭。
ACS 的特征是中性粒细胞强烈激活，与其他全身性炎症性综合征相似。在急性心肌梗死的极早期，只有一小部分中性粒细胞被大量激活，可能通过血小板-P 选择素相互作用。这种阵发性激活可能有助于闭塞性血栓形成。
