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Torgun Whre, Jan Kristian Dams, Arne Yndestad, Kjetil Taskn, Turid M. Pedersen, Camilla Smith, Bente Halvorsen, Stig S. Frland, Nils O. Solum, Pl Aukrust
Effect of activated platelets on expression of cytokines in peripheral blood mononuclear cells potential role of prostaglandin E2
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-1; (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-1 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-1 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-1 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 PGE2 related 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.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 92, 12/2004
Pages: 1358 - 1367