Am J Blood Res 2013;3(2):107-123
Original Article
Aging- and activation-induced platelet microparticles suppress apoptosis in
monocytic cells and differentially signal to proinflammatory mediator release
Elena M Vasina, Sandra Cauwenberghs, Mareike Staudt, Marion AH Feijge, Christian Weber, Rory R Koenen, Johan WM
Heemskerk
Institute 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; Vesalius Research Center, Flanders Institute for
Biotechnology (VIB), Katholieke Universiteit, Leuven, Leuven, Belgium; Institute for Cardiovascular Prevention, University of
Munich, Munich, Germany
Received December 30, 2012; Accepted March 21, 2013; Epub May 5, 2013; Published May 15, 2013
Abstract: 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 Ca2+ 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 Ca2+ 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 Ca2+ 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. (AJBR1212006).
Keywords: Aging, apoptosis, microparticles, monocytes, platelet activation, tumour necrosis factor
Address correspondence to: Johan WM Heemskerk, Department of Biochemistry, CARIM, Maastricht University, P.O. Box
616, 6200 MD Maastricht, The Netherlands. Tel: +31-43-3881671; Fax: +31-43-3884159; E-mail: jwm.
heemskerk@maastrichtuniversity.nl; Dr. Rory R Koenen, Institute for Cardiovascular Prevention, Ludwig-Maximilian-University
of Munich, Munich, Germany. Tel: +49-89-5160-4672; Fax: +49-89-5160-4352; E-mail: Rory.Koenen@med.uni-muenchen.de
Original Article
Aging- and activation-induced platelet microparticles suppress apoptosis in
monocytic cells and differentially signal to proinflammatory mediator release
Elena M Vasina, Sandra Cauwenberghs, Mareike Staudt, Marion AH Feijge, Christian Weber, Rory R Koenen, Johan WM
Heemskerk
Institute 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; Vesalius Research Center, Flanders Institute for
Biotechnology (VIB), Katholieke Universiteit, Leuven, Leuven, Belgium; Institute for Cardiovascular Prevention, University of
Munich, Munich, Germany
Received December 30, 2012; Accepted March 21, 2013; Epub May 5, 2013; Published May 15, 2013
Abstract: 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 Ca2+ 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 Ca2+ 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 Ca2+ 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. (AJBR1212006).
Keywords: Aging, apoptosis, microparticles, monocytes, platelet activation, tumour necrosis factor
Address correspondence to: Johan WM Heemskerk, Department of Biochemistry, CARIM, Maastricht University, P.O. Box
616, 6200 MD Maastricht, The Netherlands. Tel: +31-43-3881671; Fax: +31-43-3884159; E-mail: jwm.
heemskerk@maastrichtuniversity.nl; Dr. Rory R Koenen, Institute for Cardiovascular Prevention, Ludwig-Maximilian-University
of Munich, Munich, Germany. Tel: +49-89-5160-4672; Fax: +49-89-5160-4352; E-mail: Rory.Koenen@med.uni-muenchen.de
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