An Intense and Short-Lasting Burst of Neutrophil Activation Differentiates Early Acute Myocardial Infarction from Systemic Inflammatory Syndromes

Abstract

BackgroundNeutrophils 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.Methods and FindingsThe 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.ConclusionsACS 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.

Relationship between Serum Inflammatory Biomarkers and Thrombus Characteristics in Patients with ST Segment Elevation Myocardial Infarction

“…This observation is in keeping with the observed higher thromboxane A 2 levels produced upon platelet activation, which were associated with high MPO in our study. This observation is in agreement with recent findings that suggested that MPO release is the culprit lesion in STEMI [25], along with the interplay between neutrophils, platelets, and monocytes as aggregates in STEMI [26], and the short, intense burst of neutrophil activation that differentiates early acute myocardial infarction from other systemic inflammatory conditions [27]. Finally, MPO-rich thrombi and high MPO plasma levels have been associated with erythrocyte-rich thrombi, worse reperfusion and left ventricle remodeling in STEMI [28].…”

“…However, a recent study showed that neutrophil activation as assessed by MPO neutrophil content reduction is not observed after septal alcohol ablation, and may be present even with low troponin I levels, suggesting that MPO is less dependent on necrosis than CRP [27]. Therefore, high levels of MPO with low levels of CRP might be utilized as a marker of the formation of early thrombi, which are rich in platelets and neutrophils.…”

Platelet CD40 Exacerbates Atherosclerosis by Transcellular Activation of Endothelial Cells and Leukocytes

“…Recent studies report that this activation is induced by platelet-P selectin interactions inducing complete myeloperoxidase depletion in neutrophils. 47 Furthermore, in vitro studies revealed that platelets control the recruitment, activation, differentiation, and cytokine production of different CD4 + T-cell subsets. 48 We recently showed in vivo that platelet CD40L mediates the reduction of circulating Treg cells, thereby promoting the development of atherosclerosis.…”

Dependence of Level of Myeloperoxidase of Plasma of Blood on Functional State of Neutrophils at Acute Infarct of Myocardium

“…Низька активність МПО в цих клітинах асоціюється з активацією тромбоци-тів і утворенням тромбоцитарно-нейтрофиль-них агрегатів [15,23]. У більшості пацієнтів вміст МПО в плазмі крові хворих на гострий інфаркт міокарда був високим і становив 606,0±59,3 нг/мл (31,9-1870,0 нг/мл).…”