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Updated: May 11, 2026
Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation
Published on: May 23, 2025
Aging- and activation-induced platelet microparticles suppress apoptosis in monocytic cells and differentially signal
Elena M Vasina1, Sandra Cauwenberghs, Mareike Staudt
1Institute for Molecular Cardiovascular Research (IMCAR), University Hospital Aachen, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen Germany ; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Maastricht, the Netherlands.
Background:
Platelet microparticles (PM) are the most abundant cell-derived microparticles in the blood, and accumulate in thrombo-inflammatory diseases. Platelets produce PM upon aging via an apoptosis-like process and by activation with strong agonists. We previously showed that long-term treatment of monocytic cells with apoptosis-induced PM (PMap) promotes their differentiation into resident macrophages. Here we investigated shorter term effects of various types of PM on monocyte signalling and function.
Methods And Results:
Flow cytometry and scanning electron microscopy revealed that PM formed upon platelet aging (PMap) or ultra-sonication (PMsonic) expressed activated αIIbβ3 integrins and tended to assemble into aggregates. In contrast, PM formed upon platelet activation with thrombin (PMthr) or Ca(2+) ionophore (PMiono) had mostly non-activated αIIbβ3 and little aggregate formation, but had increased CD63 expression. PM from activated and sonicated platelets expressed phosphatidylserine at their surface, while only the latter were enriched in the receptors CD40L and CX3CR1. All PM types expressed P-selectin, interacted with monocytic cells via this receptor, and were internalised into these cells. The various PM types promoted actin cytoskeletal rearrangements and hydrogen peroxide production by monocytic cells. Markedly, both aging- and activation-induced PM types stimulated the phosphoinositide 3-kinase/Akt pathway, suppressing apoptosis induced by several agonists, in a P-selectin-dependent manner. On the other hand, the PM types differentially influenced monocyte signalling in eliciting Ca(2+) fluxes (particularly PMap) and in releasing secondary mediators (complement factor C5a with PMap, and pro-inflammatory tumour necrosis factor-α with PMthr).
Conclusions:
In spite of their common anti-apoptotic potential via Akt activation, aging- and activation-induced PM cause different Ca(2+) signalling events and mediator release in monocytic cells. By implication, aging and activated platelets may modulate monocyte function in different way by the shedding of different PM types.
Insights
Platelet microparticles (PM) from aging or activation affect monocytes differently. While all PM types suppress apoptosis via Akt activation, they trigger distinct signaling pathways and mediator release, influencing monocyte function uniquely.
Area of Science:
- Hematology
- Immunology
- Cell Biology
Background:
- Platelet microparticles (PM) are abundant in blood and linked to thrombo-inflammatory diseases.
- PM are generated through platelet aging (apoptosis-like) or activation.
- Previous work showed long-term PM (PMap) promotes monocyte differentiation into macrophages.
Purpose of the Study:
- Investigate short-term effects of various PM types on monocyte signaling and function.
- Characterize differences in PM generated by aging versus activation.
- Determine the impact of PM on monocyte-derived inflammatory responses.
Main Methods:
- Flow cytometry and scanning electron microscopy to analyze PM characteristics (integrin activation, CD63, phosphatidylserine, receptor expression).
- Assessed PM interaction with monocytic cells, including internalization and actin rearrangement.
- Measured monocyte hydrogen peroxide production, Ca(2+) fluxes, and release of mediators like TNF-α and C5a.
- Investigated the role of P-selectin in PM-monocyte interactions and apoptosis suppression via the Akt pathway.
Main Results:
- PM from aging (PMap) or sonication (PMsonic) showed activated αIIbβ3 and aggregate formation.
- PM from thrombin (PMthr) or ionophore (PMiono) activation had higher CD63 expression.
- All PM types expressed P-selectin, interacted with monocytes, and were internalized.
- PM promoted cytoskeletal rearrangements and H2O2 production in monocytes.
- All PM types suppressed agonist-induced apoptosis via P-selectin-dependent Akt activation.
- PMap particularly induced Ca(2+) fluxes and C5a release; PMthr released TNF-α.
Conclusions:
- Aging- and activation-induced PM share anti-apoptotic effects through Akt activation.
- Distinct PM types elicit different Ca(2+) signaling events and mediator release in monocytes.
- Platelet aging and activation modulate monocyte function through distinct PM shedding mechanisms.
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