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Proteomic analysis of human platelet-derived extracellular vesicles generated via activation by different receptors

ABSTRACT: Renowned for their role in hemostasis and thrombosis, platelets are increasingly recognized for their involvement in innate immunity, immunothrombosis and inflammatory diseases. Platelets, heterogeneous in size and molecular content, express a wide range of receptors enabling versatile activation endpoints relevant for immune functions. Upon activation, platelet release extracellular vesicles (PEVs), whose formation and molecular cargo exhibit remarkable tunability based on receptor-mediated activation or environmental cues. This study aimed to compare the immune modulatory roles of PEVs released through activation by specific platelet receptors, GPVI, CLEC-2, and thrombin-collagen (TC). Functional assays in vivo in zebrafish and using an in vitro human macrophage models highlighted distinct immune-inflammatory responses triggered by PEVs. Surprisingly, despite extensive characterization using omics analyses and basic EV particle characterization, the differences in the protein and miRNA cargo and the EV physicochemical properties between the PEV types were subtle and insufficient to precisely define their mechanism of action to distinguish a distinct functional profile. Moreover, the constitutively formed PEVs used as controls displayed a disparate activation profile from the receptor-induced PEVs.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Platelet

SUBMITTER: Mari Palviainen

LAB HEAD: Pia Siljander

PROVIDER: PXD047323 | Pride | 2024-09-19

REPOSITORIES: Pride

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