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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, RESULTS. Meshes: Amino Acid Motifs, Blood Platelets, Carrier Proteins, Crotalid Venoms, Enzyme Activation, Female, Flow Cytometry, Humans, Intracellular Signaling Peptides and Proteins, Lectins, C-Type, Male, Niacinamide, Peptides, Platelet Membrane Glycoproteins, Protein Kinase Inhibitors, Protein Structure, Tertiary, Protein-Tyrosine Kinases, Pyrimidines, Reactive Oxygen Species, Receptors, IgG, Signal Transduction, Syk Kinase, Time Factors.
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Does iTAM receptor-mediated generation of reactive oxygen species in human platelets occur via Syk-dependent and Syk-independent pathways? Context: Ligation of the platelet-specific collagen receptor, GPVI/FcRγ, causes rapid, transient disulfide-dependent homodimerization, and the production of intracellular reactive oxygen species (ROS) generated by the NADPH oxidase, linked to GPVI via TRAF4. The aim of this study was to evaluate the role of early signaling events in ROS generation following engagement of either GPVI/FcRγ or a second immunoreceptor tyrosine-based activation motif (ITAM)-containing receptor on platelets, FcγRIIa. Using an H(2) DCF-DA-based flow cytometric assay to measure intracellular ROS, we show that treatment of platelets with either the GPVI agonists, collagen-related peptide (CRP) or convulxin (Cvx), or the FcγRIIa agonist 14A2, increased intraplatelet ROS; other platelet agonists such as ADP and TRAP did not. Basal ROS in platelet-rich plasma from 14 healthy donors displayed little inter-individual variability. CRP, Cvx or 14A2 induced an initial burst of ROS within 2 min followed by additional ROS reaching a plateau after 15-20 min. The Syk inhibitor BAY61-3606, which blocks ITAM-dependent signaling, had no effect on the initial ROS burst, but completely inhibited the second phase.
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Together, these results show for the first time that ROS generation downstream of GPVI or FcγRIIa consists of two distinct phases: an initial Syk-independent burst followed by additional Syk-dependent generation. Final Decision: yes