Emerging roles for platelets as immune and inflammatory cells

Morrell, Craig N.; Aggrey, Angela; Chapman, Lesley; Modjeski, Kristina L.

doi:10.1182/blood-2013-11-462432

Cited by 611 publications

(540 citation statements)

References 165 publications

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“…Indeed, miRNA-containing platelet MPs are internalized by endothelial cells, thereby altering the stability of mRNA in the recipient (16). Platelets are also active participants in immunity (17)(18)(19)(20); platelet MPs are found in inflammatory conditions (1,17,21) and are ideally positioned to interact with immune cells.…”

mentioning

confidence: 99%

Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase A ₂ -IIA

Duchez

Boudreau

Naika

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

200

174

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Platelets are anucleated blood elements highly potent at generating extracellular vesicles (EVs) called microparticles (MPs). Whereas EVs are accepted as an important means of intercellular communication, the mechanisms underlying platelet MP internalization in recipient cells are poorly understood. Our lipidomic analyses identified 12(S)-hydroxyeicosatetranoic acid [12(S)-HETE] as the predominant eicosanoid generated by MPs. Mechanistically, 12(S)-HETE is produced through the concerted activity of secreted phospholipase A2 IIA (sPLA2-IIA), present in inflammatory fluids, and platelet-type 12-lipoxygenase (12-LO), expressed by platelet MPs. Platelet MPs convey an elaborate set of transcription factors and nucleic acids, and contain mitochondria. We observed that MPs and their cargo are internalized by activated neutrophils in the endomembrane system via 12(S)-HETE. Platelet MPs are found inside neutrophils isolated from the joints of arthritic patients, and are found in neutrophils only in the presence of sPLA2-IIA and 12-LO in an in vivo model of autoimmune inflammatory arthritis. Using a combination of genetically modified mice, we show that the coordinated action of sPLA2-IIA and 12-LO promotes inflammatory arthritis. These findings identify 12(S)-HETE as a trigger of platelet MP internalization by neutrophils, a mechanism highly relevant to inflammatory processes. Because sPLA2-IIA is induced during inflammation, and 12-LO expression is restricted mainly to platelets, these observations demonstrate that platelet MPs promote their internalization in recipient cells through highly regulated mechanisms.

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mentioning

confidence: 99%

Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase A ₂ -IIA

Duchez

Boudreau

Naika

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

200

174

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“…They play an important role not only in hemostasis, but also in angiogenesis, inflammation, allergic reactions and repair and renewal of tissues and contain mediators which lead to strong inflammatory response (1). The platelet volume is specified during formation of platelets from megakariocytes in the bone marrow.…”

Section: Introductionmentioning

confidence: 99%

Reduction in mean platelet volume in children with acute bronchiolitis

et al. 2016

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Aim: Platelets which are known to play a role in inflamation change their shapes when they are activated and this change is reflected in mean platelet volume and platelet distribution width values. Therefore, the mean platelet volume and platelet distribution width values are considered to be beneficial parameters for the diagnosis and treatment of many inflammatory diseases. The aim of the study was to evaluate platelet volume indices in children with acute bronchiolitis. Material and Methods:A total of 514 infants who were below the age of 2 years old were evaluated in this study. Three hundred thirteen of these infants were diagnosed with acute bronchiolitis patients and 201 were healthy children. The patients were separated into four groups as mild, moderate, severe bronchiolitis and the control patient group. The groups were evaluated in terms of significant differences in the values of mean platelet volume and platelet distribution width. A p value of <0.05 was considered statistically significant for all results. Results:The mean platelet volume was found to be 6.8±0.6 fL in the patients with mild bronchiolitis attack, 6.7±0.6 fL in the patients with moderate bronchiolitis attack, 6.5±0.5 fL in the patients with severe bronchiolitis attack and 7.3±1.1 fL in the control group. The mean platalet volume was statistically significantly lower in the mild, moderate and severe bronchiolitis attack groups compared to the control group (p=0.000). The platelet distribution width was found to be 17.2%±0.83 in the mild bronchiolitis attack group, 17.1%±0.96 in the moderate bronchiolitis attack group, 17.3%±0.87 in the severe bronchiolitis attack group and 16.9±1.6% in the control patient group. This difference was not statistically significant (p=0.159). The platelet count was statistically significantly higher in the mild, moderate and severe bronchiolitis attack groups compared to the control group (p=0.000).

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“…Moreover, platelets can physically interact with adjacent monocytes and dendritic cells (DCs) via receptor-ligand interactions, particularly CD154/ CD40 crosstalk, contributing to enhanced antigen presentation and adaptive immune responses. 3,4 CD154 (CD40 ligand, CD40L) is a membrane bound protein belonging to the TNF superfamily. Engagement of CD40 by its ligand CD154 plays a central role in mediating the interaction between antigen-presenting cells (APCs) and lymphocytes.…”

Section: Introductionmentioning

confidence: 99%

Platelets promote allergic asthma through the expression of CD154

et al. 2014

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Platelet activation is associated with multiple immune responses and the pathogenesis of various immune-related diseases. However, the exact role and the underlying mechanism of platelets in the progression of allergic asthma remain largely unclear. In this study, we demonstrate that during antigen sensitization, platelets can be activated by ovalbumin (OVA) aerosol via the upregulation of CD154 (CD40L) expression. Platelet transfer promoted allergic asthma progression by inducing more severe leukocyte infiltration and lung inflammation, elevated IgE production and strengthened T helper 2 (Th2) responses in asthma-induced mice. Accordingly, platelet depletion compromised allergic asthma progression. Cd154-deficient platelets failed to promote asthma development, indicating the requirement of CD154 for platelets to promote asthma progression. The mechanistic study showed that platelets inhibited the induction of Foxp3 1 regulatory T cells both in vivo and in vitro at least partially through CD154, providing an explanation for the increase of Th2 responses by platelet transfer. Our study reveals the previously unknown role of platelet CD154 in the promotion of asthma progression by polarizing Th2 responses and inhibiting regulatory T-cell generation and thus provides a potential clue for allergic disease interventions.

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Emerging roles for platelets as immune and inflammatory cells

Cited by 611 publications

References 165 publications

Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase A ₂ -IIA

Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase A ₂ -IIA

Reduction in mean platelet volume in children with acute bronchiolitis

Platelets promote allergic asthma through the expression of CD154

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Emerging roles for platelets as immune and inflammatory cells

Cited by 611 publications

References 165 publications

Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase A 2 -IIA

Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase A 2 -IIA

Reduction in mean platelet volume in children with acute bronchiolitis

Platelets promote allergic asthma through the expression of CD154

Contact Info

Product

Resources

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Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase A ₂ -IIA

Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase A ₂ -IIA