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Thrombin-induced lysosomal exocytosis in human platelets is dependent on secondary activation by ADP and regulated by endothelial-derived substances

Sodergren, Anna L. (författare)
Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden
Holm, Ann-Charlotte B. Svensson (författare)
Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden
Ramström, Sofia, 1973- (författare)
Linköpings universitet,Avdelningen för mikrobiologi och molekylär medicin,Medicinska fakulteten,Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden
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Lindström, Eva G. (författare)
Department of Medical and Health Sciences, Faculty of Health Sciences, Linkoöping University, Linköping, Sweden
Grenegård, Magnus, 1963- (författare)
Linköpings universitet,Örebro universitet,Institutionen för medicinska vetenskaper,Department of Medical and Health Sciences, Faculty of Health Sciences, Linkoöping University, Linköping, Sweden; Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden,Avdelningen för läkemedelsforskning,Medicinska fakulteten,University of Örebro, Sweden
Öllinger, Karin (författare)
Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Region Östergötland, Klinisk patologi och klinisk genetik,Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden
Lindström, Eva (författare)
Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten
Södergren, Anna (författare)
Linköpings universitet,Avdelningen för mikrobiologi och molekylär medicin,Medicinska fakulteten
Svensson Holm, Ann-Charlotte (författare)
Linköpings universitet,Biologi,Tekniska fakulteten
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 (creator_code:org_t)
Taylor & Francis, 2016
2016
Engelska.
Ingår i: Platelets. - : Taylor & Francis. - 0953-7104 .- 1369-1635. ; 27:1, s. 86-92
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)
NATURAL SCIENCES  -- Biological Sciences (hsv//eng)
NATURVETENSKAP  -- Biologiska vetenskaper (hsv//swe)

Nyckelord

ADP receptors
endothelium
exocytosis
lysosome
platelet physiology
protease activated receptors (PAR)
thrombin
ADP receptors; endothelium; exocytosis; lysosome; platelet physiology; protease activated receptors (PAR); thrombin

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