Reverse correlations of collagen-dependent platelet aggregation and adhesion with GPVI shedding during storage
Platelet receptor GPVI plays an important role in platelet firm adhesion to site of vascular injury. Receptor ligation with collagen, in company with other agonist/receptor interactions, augments inside out signaling pathways leading to platelet aggregation and thrombus formation. As GPVI expression is significantly modulated by ectodomain shedding, this study aimed to examine whether GPVI shedding functionally affects collagen-mediated platelet activation during storage. 6 PRP-platelet concentrates were subjected to adhesion analysis on collagen matrix under mild stirring condition as well as collagen-induced aggregation on day 1, 3 and 5 post-storage. Concurrently, platelet supernatants of same samples were fractionated by ultra-centrifugation and obtained micro-particle-free samples were subjected to western blot analysis for the evaluation of GPVI shedding. We showed a direct correlation between collagen-dependent platelet aggregation and adhesion (r = 0.8, p = 0.0001). The increasing levels of GPVI shedding during storage were in reverse correlation with collagen-induced platelet aggregation (r = − 0.82, p = 0.0004) which was significantly reducing during storage. Platelet adhesion to collagen matrix significantly decreased post-storage while it was also reversely correlated with the levels of GPVI shedding during 5 days storage of platelets (r = − 0.69, p = 0.002). Data presented here demonstrated that progressive shedding of surface adhesion receptor GPVI can affect its functional activities in stored platelets. Thereby considering the crucial role of GPVI in platelet adhesion to the site of injury, whether the therapeutic efficacy of banked platelet products could be influenced by storage-dependent shedding of this receptor, remains to be answered in future studies.
KeywordsAdhesion Aggregation Collagen GPVI Platelet concentrates, Platelet-rich plasma (PRP), Platelet storage lesion Shedding
MG supervised and designed the study, did the experiments, analyzed the data and wrote the paper. EH did some experiments, helped with analyzing data and writing the paper. PB did some experiments.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest. This work was part of Dr. Ghasemzadeh’s approved project (No. 1394-01-33-1861) which is also considered as research material for a PhD student thesis supported by Iranian blood transfusion organization and High Institute for Research and Education in Transfusion Medicine in Iran.
Ethical approval for this research was provided by ethic committee in High Institute for Research and Education in Transfusion Medicine in accordance with national legislation and local rules.
Informed consent was obtained from all individual participants included in the study.
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