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CLEC-2-dependent activation of mouse platelets is weakly inhibited by cAMP but not by cGMP.
- Source :
-
Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2014 Apr; Vol. 12 (4), pp. 550-9. - Publication Year :
- 2014
-
Abstract
- Background: The activation of platelet CLEC-2 by podoplanin on lymphatic endothelial cells (LECs) has a critical role in prevention of mixing of lymphatic and blood vasculatures during embryonic development. Paradoxically, LECs release cAMP and cGMP-elevating agents, prostacyclin (PGI2 ) and nitric oxide (NO), respectively, which are powerful inhibitors of platelet activation. This raises the question of how podoplanin is able to activate CLEC-2 in the presence of the inhibitory cyclic nucleotides.<br />Objectives: We investigated the influence of cyclic nucleotides on CLEC-2 signaling in platelets.<br />Methods: We used rhodocytin, CLEC-2 monoclonal antibody, LECs and recombinant podoplanin as CLEC-2 agonists on mouse platelets. The effects of the cyclic nucleotide-elevating agents PGI2 , forskolin and the NO-donor GSNO were assessed with light transmission aggregometry, flow cytometry, protein phosphorylation and fluorescent imaging of platelets on LECs.<br />Results: We show that platelet aggregation induced by CLEC-2 agonists is resistant to GSNO but inhibited by PGI2 . The effect of PGI2 is mediated through decreased phosphorylation of CLEC-2, Syk and PLCγ2. In contrast, adhesion and spreading of platelets on recombinant podoplanin, CLEC-2 antibody and LECs is not affected by PGI2 and GSNO. Consistent with this, CLEC-2 activation of Rac, which is required for platelet spreading, is not altered in the presence of PGI2 .<br />Conclusions: The present results demonstrate that platelet adhesion and activation on CLEC-2 ligands or LECs is maintained in the presence of PGI2 and NO.<br /> (© 2014 International Society on Thrombosis and Haemostasis.)
- Subjects :
- Animals
Blood Platelets drug effects
Calcium metabolism
Cell Adhesion
Epoprostenol metabolism
Mice
Mice, Inbred C57BL
Nitric Oxide metabolism
Platelet Adhesiveness
Platelet Aggregation
Viper Venoms metabolism
Blood Platelets cytology
Cyclic AMP metabolism
Cyclic GMP metabolism
Lectins, C-Type metabolism
Membrane Glycoproteins metabolism
Platelet Activation
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7836
- Volume :
- 12
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of thrombosis and haemostasis : JTH
- Publication Type :
- Academic Journal
- Accession number :
- 24460629
- Full Text :
- https://doi.org/10.1111/jth.12514