Effect of activated platelets on expression of cytokines in peripheral blood mononuclear cells – potential role of prostaglandin E2

Torgun Wæhre; Jan Kristian Damås; Arne Yndestad; Kjetil Taskén; Turid M. Pedersen; Camilla Smith; Bente Halvorsen; Stig S. Frøland; Nils O. Solum; Pål Aukrust

doi:10.1160/TH04-03-0146

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(06): 1358-1367
DOI: 10.1160/TH04-03-0146

Platelets and Blood Cells

Schattauer GmbH

Effect of activated platelets on expression of cytokines in peripheral blood mononuclear cells – potential role of prostaglandin E₂

Authors

Torgun Wæhre

¹Research Institute of Internal Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

²Department of Cardiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Jan Kristian Damås

¹Research Institute of Internal Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

²Department of Cardiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Arne Yndestad

¹Research Institute of Internal Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Kjetil Taskén

⁴Department of Medical Biochemistry, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Turid M. Pedersen

¹Research Institute of Internal Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Camilla Smith

¹Research Institute of Internal Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Bente Halvorsen

¹Research Institute of Internal Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Stig S. Frøland

¹Research Institute of Internal Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

³Section of Clinical Immunology and Infectious Diseases, Rikshospitalet University Hospital, Oslo, Norway
Nils O. Solum

¹Research Institute of Internal Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
Pål Aukrust

¹Research Institute of Internal Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

³Section of Clinical Immunology and Infectious Diseases, Rikshospitalet University Hospital, Oslo, Norway

Abstract

Summary

Platelets may act as inflammatory cells. To study the effects of soluble and cell-bound platelet factors on the expression of several cytokines and related mediators in leukocytes, peripheral blood mononuclear cells (PBMC) were incubated with platelet-free supernatants from SFLLRN-activated platelet-rich plasma (PRP) or SFLLRN-activated PRP in itself. Our main findings were: (i) the gene expression of several chemokines and some cytokines were markedly increased by both activated PRP and supernatants, as also confirmed at the protein level for IL-6, IL-8 and MIP-1α; (ii) the selective protein kinase A type I (PKAI) antagonist Rp-8-Br-cAMP reduced this platelet-induced expression of IL-6, IL-8 and MIP-1α in PBMC, suggesting a role of cAMP/PKAI mediated mechanisms in this interaction; (iii) PGE₂ dose-dependently increased the release of IL-6, IL-8 and MIP-1α from PBMC mimicking the effect of activated platelets. Furthermore, activated platelets released comparable amounts of PGE₂, suggesting that platelet-derived PGE₂ could interact with PBMC in co-cultures; (iv) IL-10 inhibited the platelet-inducing effect on IL-6, IL-8 and MIP-1α in PBMC, and notably, the addition PGE₂ totally abolished this IL-10 effect suggesting that the suppressive effect of IL-10 on the plateletinduced activation of PBMC might at least partly involve PGE₂related mechanisms. The present study supports a view of platelets as inflammatory cells, and suggests a potential role of platelet-derived PGE₂ in platelet-induced inflammatory responses.

Keywords

Platelets - inflammation - interleukin-6 - prostaglandin E₂ - mononuclear cells

Full Text

References

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