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.
Highlights
Platelet and endothelial activation, associated with plaque instability, are important mechanisms in the pathogenesis of acute coronary syndromes (ACS) [1,2,3,4,5]
ACS are characterized by intense neutrophil activation, like other systemic inflammatory syndromes
We have studied neutrophil MPO content and its relation to platelet and monocyte activation in patients with segment T elevation myocardial infarction (STEMI), with non elevation myocardial infarction (NSTEMI) and with unstable angina, sampled before any therapeutic intervention
Summary
Platelet and endothelial activation, associated with plaque instability, are important mechanisms in the pathogenesis of acute coronary syndromes (ACS) [1,2,3,4,5]. Given the short life of circulating neutrophils the release of their MPO content can only reflect the effects of stimuli active during the previous 6–8 hours of their life time. Measurement of neutrophil MPO content at different times after the onset of symptoms could provide information on the time-course as well as clues on distinctive features of inflammatory stimuli associated with coronary instability. We have studied neutrophil MPO content and its relation to platelet and monocyte activation in patients with segment T elevation myocardial infarction (STEMI), with non elevation myocardial infarction (NSTEMI) and with unstable angina, sampled before any therapeutic intervention. We investigated whether specific features of neutrophil activation characterize patients with acute coronary syndromes (ACS) compared to stable angina and to systemic inflammatory diseases
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