Circulating Monocyte-Platelet Aggregates Are a More Sensitive Marker of In Vivo Platelet Activation Than Platelet Surface P-Selectin

Abstract

Background-Platelet surface P-selectin is considered the "gold standard" marker of platelet activation. Degranulated, P-selectin-positive platelets, however, aggregate with leukocytes in vitro and rapidly lose surface P-selectin in vivo. Methods and Results-Flow cytometric tracking of autologous, biotinylated platelets in baboons enabled us to directly demonstrate for the first time in vivo that (1) infused degranulated platelets very rapidly form circulating aggregates with monocytes and neutrophils, and (2) 30 minutes after infusion of the degranulated platelets, the percentage of circulating monocytes aggregated with infused platelets persist at high levels, whereas the percentage of circulating neutrophils aggregated with infused platelets and the platelet surface P-selectin of nonaggregated infused platelets return to baseline. We therefore performed 2 clinical studies in patients with acute coronary syndromes. First, after percutaneous coronary intervention (nϭ10), there was an increased number of circulating monocyte-platelet (and to a lesser extent, neutrophil-platelet) aggregates but not P-selectin-positive platelets. Second, of 93 patients presenting to an Emergency Department with chest pain, patients with acute myocardial infarction (AMI) (nϭ9) had more circulating monocyteplatelet aggregates (34.2Ϯ10.3% [meanϮSEM]) than patients with no AMI (nϭ84, 19.3Ϯ1.4%, PϽ0.05) and normal control subjects (nϭ10, 11.5Ϯ0.8%, PϽ0.001). Circulating P-selectin-positive platelets, however, were not increased in chest pain patients with or without AMI.

Platelets stimulated by IgG-coated surfaces bind and activate neutrophils through a selectin-dependent pathway

“…A similar observation was made by Broberg and Nygren [32]. We observed, in accordance with Michelsson and coworkers [54], that the time scale was important for the detection of P-selectin. For instance, when prestimulated viable platelet fractions were stored for longer time (>10 min), the stimulatory effect on the neutrophil respiratory burst became markedly reduced.…”

“…Frenette and co-workers demonstrated the presence of biologically active PSGL-1 on platelet membranes, although at lower densities than on neutrophils [51]. In our study, the presence of PSGL-1 on neutrophil and platelet membranes was confirmed by fluorescence microscopy Since P-selectin is rapidly (minutes) released from activated platelets during activation [52,53], and activated platelets quickly form aggregates with leukocytes in vivo, it has been suggested that the formation of platelet-leukocyte aggregates is a better marker of platelet activation than P-selectin expression [54]. Large portion of the neutrophil and platelet populations is actually circulating aggregates with enhanced inflammatory capabilities.…”

Inflammation-related effects of adjuvant influenza A vaccination on platelet activation and cardiac autonomic function

“…Moreover, in previous studies, MPAs have been shown to be associated with acute coronary events [8,24].…”

The Uncoupling of Monocyte–Platelet Interactions from the Induction of Proinflammatory Signaling in Monocytes

“…E levated numbers of circulating blood monocyte-platelet complexes were suggested to play a role in the pathogenesis of acute coronary syndromes and the earliest events of atherosclerosis (1)(2)(3). Increased monocyte-platelet complexes have also been observed in a number of diseases, including type 1 diabetes (4), rheumatoid arthritis (5), and end-stage renal disease (6), suggesting an important role in the pathogenesis of inflammatory diseases.…”