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

Peter Gunnarsson; Louise Levander; Peter Påhlsson; Magnus Grenegård

doi:10.1160/TH09-03-0156

Thrombosis and Haemostasis, Table of Contents

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

Authors

Peter Gunnarsson

¹Division of Drug Research, Linköping University, Linköping, Sweden
Louise Levander

²Division of Cell Biology, Linköping University, Linköping, Sweden
Peter Påhlsson

²Division of Cell Biology, Linköping University, Linköping, Sweden
Magnus Grenegård

¹Division of Drug Research, Linköping University, Linköping, Sweden

Abstract

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

Full Text

References

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