Dataset Information

Discriminating young platelets on human leukocyte antigen-I expression highlights their extremely high reactivity potential.

ABSTRACT:

Background

The platelet population is heterogeneous, with different subsets that differ on the basis of their function and reactivity. An intrinsic factor participating in this difference of reactivity could be the platelet age. The lack of relevant tools allowing a formal identification of young platelets prevents so far to draw solid conclusions regarding platelet reactivity. We recently reported that human leukocyte antigen-I (HLA-I) molecules are more expressed on human young platelets.

Objectives

The aim of this study was to assess platelet reactivity according to their age based on HLA-I expression level.

Methods

Platelet activation was assessed by flow cytometry (FC) for different platelet subsets based on their HLA-I expression. These populations were further cell sorted and their intrinsic properties were determined by FC and electron microscopy (EM). Statistical analyses were performed with GraphPad Prism 5.02 software using two-way ANOVA followed by a Tukey post hoc test.

Results

HLA-I expression level allowed the identification of 3 platelet subpopulations regarding to their age (HLA low, dim, and high). HLA-I was reliable to guide platelet cell sorting and highlighted the features of young platelets in the HLA-I^high population. In response to different soluble agonists, HLA-I^high platelets were the most reactive subset as shown by the level of P-selectin secretion and fibrinogen binding assessed by flow cytometry. Moreover, the highest capacity of HLA-I^high platelets to simultaneously express annexin-V and von Willebrand factor or activated αIIbβ3 after coactivation with TRAP and CRP indicated that the procoagulant feature of platelets was age-related.

Conclusion

The young HLA-I^high population is the most reactive and prone to become procoagulant. These results open up new perspectives to investigate deeply the role of young and old platelets.

SUBMITTER: Angenieux C

PROVIDER: S-EPMC10031328 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Discriminating young platelets on human leukocyte antigen-I expression highlights their extremely high reactivity potential.

Angénieux Catherine C Couvidou Adèle A Brouard Nathalie N Eckly Anita A Dupuis Arnaud A Mangin Pierre H PH Maître Blandine B

Research and practice in thrombosis and haemostasis 20230101 1

<h4>Background</h4>The platelet population is heterogeneous, with different subsets that differ on the basis of their function and reactivity. An intrinsic factor participating in this difference of reactivity could be the platelet age. The lack of relevant tools allowing a formal identification of young platelets prevents so far to draw solid conclusions regarding platelet reactivity. We recently reported that human leukocyte antigen-I (HLA-I) molecules are more expressed on human young platele ...[more]

PMID: 36970736

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Project description:AbstractMechanisms of proteostasis in anucleate circulating platelets are unknown and may regulate platelet function. We investigated the hypothesis that plasma-borne growth factors/hormones (GFHs) maintain constitutive translation in circulating platelets to facilitate reactivity. Bio-orthogonal noncanonical amino acid tagging (BONCAT) coupled with liquid chromatography-tandem mass spectrometry analysis revealed constitutive translation of a broad-spectrum translatome in human platelets dependent upon plasma or GFH exposure, and in murine circulation. Freshly isolated platelets from plasma showed homeostatic activation of translation-initiation signaling pathways: phosphorylation of p38/ERK upstream kinases, essential intermediate MNK1/2, and effectors eIF4E/4E-BP1. Plasma starvation led to loss of pathway phosphorylation, but it was fully restored with 5-minute stimulation by plasma or GFHs. Cycloheximide or puromycin infusion suppressed ex vivo platelet GpIIb/IIIa activation and P-selectin exposure with low thrombin concentrations and low-to-saturating concentrations of adenosine 5'-diphosphate (ADP) or thromboxane analog but not convulxin. ADP-induced thromboxane generation was blunted by translation inhibition, and secondary-wave aggregation was inhibited in a thromboxane-dependent manner. Intravenously administered puromycin reduced injury-induced clot size in cremaster muscle arterioles, and delayed primary hemostasis after tail tip amputation but did not delay neither final hemostasis after subsequent rebleeds, nor final hemostasis after jugular vein puncture. In contrast, these mice were protected from injury-induced arterial thrombosis and thrombin-induced pulmonary thromboembolism (PE), and adoptive transfer of translation-inhibited platelets into untreated mice inhibited arterial thrombosis and PE. Thus, constitutive plasma GFH-driven translation regulates platelet G protein-coupled receptor reactivity to balance hemostasis and thrombotic potential.

Dataset Information

Discriminating young platelets on human leukocyte antigen-I expression highlights their extremely high reactivity potential.

Background

Objectives

Methods

Results

Conclusion

Publications

Discriminating young platelets on human leukocyte antigen-I expression highlights their extremely high reactivity potential.

Similar Datasets

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