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Thrombin-induced lysosomal exocytosis in human platelets is dependent on secondary activation by ADP and regulated by endothelial-derived substances
Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.ORCID iD: 0000-0002-1920-3962
Department of Medical and Health Sciences, Faculty of Health Sciences, Linkoöping University, Linköping, Sweden.
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2016 (English)In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 27, no 1, p. 86-92Article in journal (Refereed) Published
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Abstract [en]

Exocytosis of lysosomal contents from platelets has been speculated to participate in clearance of thrombi and vessel wall remodelling. The mechanisms that regulate lysosomal exocytosis in platelets are, however, still unclear. The aim of this study was to identify the pathways underlying platelet lysosomal secretion and elucidate how this process is controlled by platelet inhibitors. We found that high concentrations of thrombin induced partial lysosomal exocytosis as assessed by analysis of the activity of released N-acetyl--glucosaminidase (NAG) and by identifying the fraction of platelets exposing the lysosomal-associated membrane protein (LAMP)-1 on the cell surface by flow cytometry. Stimulation of thrombin receptors PAR1 or PAR4 with specific peptides was equally effective in inducing LAMP-1 surface expression. Notably, lysosomal exocytosis in response to thrombin was significantly reduced if the secondary activation by ADP was inhibited by the P2Y(12) antagonist cangrelor, while inhibition of thromboxane A(2) formation by treatment with acetylsalicylic acid was of minor importance in this regard. Moreover, the NO-releasing drug S-nitroso-N-acetyl penicillamine (SNAP) or the cyclic AMP-elevating eicosanoid prostaglandin I-2 (PGI(2)) significantly suppressed lysosomal exocytosis. We conclude that platelet inhibitors that mimic functional endothelium such as PGI(2) or NO efficiently counteract lysosomal exocytosis. Furthermore, we suggest that secondary release of ADP and concomitant signaling via PAR1/4- and P2Y(12) receptors is important for efficient platelet lysosomal exocytosis by thrombin.

Place, publisher, year, edition, pages
Taylor & Francis, 2016. Vol. 27, no 1, p. 86-92
Keywords [en]
ADP receptors, endothelium, exocytosis, lysosome, platelet physiology, protease activated receptors (PAR), thrombin
National Category
Hematology
Identifiers
URN: urn:nbn:se:oru:diva-48481DOI: 10.3109/09537104.2015.1042446ISI: 000368717700011PubMedID: 25970449Scopus ID: 2-s2.0-84955347294OAI: oai:DiVA.org:oru-48481DiVA, id: diva2:906036
Funder
Swedish Research Council
Note

Funding Agency:

County Council of Östergötland

Available from: 2016-02-23 Created: 2016-02-23 Last updated: 2019-03-26Bibliographically approved

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Ramström, SofiaGrenegård, Magnus

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