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Thromb Haemost 2009; 102(04): 694-703
DOI: 10.1160/TH09-03-0156
Platelets and Blood Cells
Schattauer GmbH

α1-acid glycoprotein (AGP)-induced platelet shape change involves the Rho/Rho kinase signalling pathway

Peter Gunnarsson
1   Division of Drug Research, Linköping University, Linköping, Sweden
,
Louise Levander
2   Division of Cell Biology, Linköping University, Linköping, Sweden
,
Peter Påhlsson
2   Division of Cell Biology, Linköping University, Linköping, Sweden
,
Magnus Grenegård
1   Division of Drug Research, Linköping University, Linköping, Sweden
› Author AffiliationsFinancial support: Financial support was provided by the Östergötland County Council (LIO-5509), the Health Research Council of Southeast Sweden (F 2001–305), and the Cardiovascular Inflammation Research Centre (CIRC) in Linköping, Sweden.
Further Information

Publication History

Received: 09 March 2009

Accepted after major revision: 10 May 2009

Publication Date:
24 November 2017 (online)

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Summary

α1-acid glycoprotein (AGP) is an acute-phase protein that contributes to inflammation processes.The role of AGP in platelet activation and thrombosis is, however, largely unknown.Therefore, we thoroughly investigated the effects of AGP on human platelets. Platelets were isolated from healthy volunteers and subsequently exposed to AGP. Platelet responses were monitored as change in light transmission, intracellular calcium concentration, light microscopy and protein phosphorylation by Western blot.We found that AGP induced platelet shape change independently of a second release of adenine nucleotides or thromboxane A2, and that effect was abolished by endotheliumderived platelet inhibitors such as nitric oxide (NO) and adenosine. Furthermore,AGP triggered a minor calcium response and a pronounced Rho/Rho-kinase-dependent increase in Thr696 phosphorylation of myosin phosphatase target subunit 1 (MYPT1). Moreover, the Rho/Rho-kinase inhibitor Y-27632 significantly decreased the AGP-induced shape change.The results also showed that the AGP-elicited shape change was antagonised by pretreatment with low doses of collagen and thrombospondin-1.Our results describe a novel mechanism by whichAGP stimulates platelet shape change via activation of the Rho/Rhokinase signalling pathway. Physiological important platelet inhibitors, such as NO, completely counterbalance the effect of AGP. Hence, the present study indicates that AGP directly contributes to platelet activation,which in turn might have an impact in physiological haemostasis and/or pathological thrombosis.

Keywords

α1-acid glycoprotein - platelets - Rho-kinase - shape change
 

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