Proteomics: A Tool to Study Platelet Function

Abstract

Platelets are components of the blood that are highly reactive, and they quickly respond to multiple physiological and pathophysiological processes. In the last decade, it became clear that platelets are the key components of circulation, linking hemostasis, innate, and acquired immunity. Protein composition, localization, and activity are crucial for platelet function and regulation. The current state of mass spectrometry-based proteomics has tremendous potential to identify and quantify thousands of proteins from a minimal amount of material, unravel multiple post-translational modifications, and monitor platelet activity during drug treatments. This review focuses on the role of proteomics in understanding the molecular basics of the classical and newly emerging functions of platelets. including the recently described role of platelets in immunology and the development of COVID-19.The state-of-the-art proteomic technologies and their application in studying platelet biogenesis, signaling, and storage are described, and the potential of newly appeared trapped ion mobility spectrometry (TIMS) is highlighted. Additionally, implementing proteomic methods in platelet transfusion medicine, and as a diagnostic and prognostic tool, is discussed.

Platelets derived citrullinated proteins and microparticles are potential autoantibodies ACPA targets in RA patients

“…Platelets are highly specialized cells and their activation involves a series of rapid rearrangements in the cytoskeleton. In this context, we hypothesized that the citrullination may modify the protein’s functional properties regulating their actin dynamics, similar to the functions of other PTMs present in the actin cytoskeleton like acetylation, phosphorylation, tyrosination and polyglutamylation ( 22 , 24 , 44 ). Furthermore, upon stimulation by various dysregulated molecules in the synovium and circulation, platelet could quick release immunostimulatory microparticals and intracellular citrullinated proteins in their environment, the exposed citrullinated proteins recognition by ACPA leading to formation of inflammatory immune complexes.…”

Socratic Lectures 8

“…The circulating platelets are also constantly patrolling with a "mission" of protecting from pathogens. Their molecular "equipment" for this purpose is versatile, with a plethora of pattern recognition receptors reactive against the diverse pathogen-associated molecular patterns (such as lipoproteins, lipopolysaccharides, or nucleic acids) or the damage-associated molecular patterns (Shevchuk et al, 2021). When sensing the bacterial presence, the platelet membrane receptors interact with the molecules on the bacterial surface or secreted from the bacterial cell, directly or indirectly, using the host-originating proteins for the "bridging".…”

Where the Action Is—Leukocyte Recruitment in Atherosclerosis

“…Upon activation, platelets undergo shape change and increase surface expression of P-selectin and CD40L, while integrin αIIbβ3 adopts its active conformation ( 333 ). Such activated circulating platelets were shown to readily bind to EC and monocytes, deposit the chemokines CCL5 and CXCL4 (also known as PF4) on both EC and monocytes and subsequently promote leukocyte accumulation and atherosclerotic lesion formation in the arterial intima, notably already prior to the development of manifest atherosclerotic lesions ( 25 , 334 ).…”