An intense and short-lasting burst of neutrophil activation differentiates early acute myocardial infarction from systemic inflammatory syndromes.

An intense and short-lasting burst of neutrophil activation differentiates early acute myocardial infarction from systemic inflammatory syndromes.
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DOI:
10.1371/journal.pone.0039484
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Maseri A
Maseri A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Maugeri N;Rovere-Querini P;Evangelista V;Godino C;Demetrio M;Baldini M;Figini F;Coppi G;Slavich M;Camera M;Bartorelli A;Marenzi G;Campana L;Baldissera E;Sabbadini MG;Cianflone D;Tremoli E;D'Angelo A;Manfredi AA;Maseri A

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中性粒细胞参与血栓的形成。我们调查了急性冠脉综合征(ACS)患者与稳定型心绞痛和全身性炎症性疾病患者中性粒细胞活化的特点。用流式细胞仪测定了330例急性冠脉综合征(ACS)、69例慢性稳定型心绞痛(CSA)、50例非感染性(急性骨折)、感染性(脓毒症)或自身免疫性疾病(大、小血管系统性脉管炎、类风湿关节炎)患者外周血中中性粒细胞髓过氧化物酶(MPO)含量。还对4名患者在无菌急性心肌损伤(隔膜酒精中毒)前后进行了研究。138名健康献血者被平行研究。MPO含量正常的中性粒细胞在对照组中为96%,在隔膜酒精中毒患者中为92%,在CsA患者中为91%,但在不稳定心绞痛和急性心肌梗死(STEMI和NSTEMI)患者中仅为35%和30%,而巨细胞动脉炎、急性骨折和严重脓毒症患者的中性粒细胞比例分别为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出现后的前4小时内MPO完全耗尽,这一特征在其他任何一组患者中都没有观察到。β耗竭与血小板活化有关,表现为P-选择素表达、白细胞MPO-2整合素的激活和反式激活以及血小板中性粒细胞和单核细胞聚集的形成。在小鼠体内注射活化的血小板,在大约50%的中性粒细胞中产生一过性的、P-选择素依赖的、完全的MPO耗竭。像其他全身炎症综合征一样,急性冠脉综合征以中性粒细胞的强烈激活为特征。在急性心肌梗死的早期阶段,只有中性粒细胞亚群被大量激活,可能是通过血小板-P选择素的相互作用。这种阵发性激活可能导致闭塞性血栓形成。
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.
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