Background: Protease-activated receptors (PARs) are a unique class of G-protein-coupled receptors, which are activated by proteolytic cleavage of the amino terminus of the receptor itself. Although expression of the PAR1, which is typically activated by thrombin, on human eosinophils has been demonstrated, no effect of thrombin on eosinophil function has been shown yet. Thus we investigated whether thrombin affects eosinophil migration in vitro. Methods: Eosinophils were obtained from venous blood of healthy donors. Cell migration was studied by micropore filter assays. Involvement of PARs in thrombin-dependent migration was tested functionally using selective agonist peptides for PARs and a cleavage blocking PAR1 antibody. Results: Thrombin significantly stimulated eosinophil chemotaxis in a dose-dependent manner. This effect was mimicked by the PAR1 but not the PAR2 agonist and was reversed by the cleavage blocking PAR1 antibody. Checkerboard experiments indicated that eosinophil migration depends on the presence of thrombin in a concentration gradient. Conclusions: Data suggest that activation of PAR1 by thrombin stimulates directed migration of human eosinophils and thereby may affect eosinophils in tissue and allergic inflammation.

Giembycz MA, Lindsay MA: Pharmacology of the eosinophil. Pharmacol Rev 1999;51:213–340.
Moritani C, Ishioka S, Haruta Y, Kambe M, Yamakido M: Activation of platelets in bronchial asthma. Chest 1998;113:452–458.
Fujisawa T, Fujisawa R, Kato Y, Nakayama T, Morita A, Katsumata H, Nishimori H, Iguchi K, Kamiya H, Gray PW, Chantry D, Suzuki R, Yoshie O: Presence of high contents of thymus and activation-regulated chemokine in platelets and elevated plasma levels of thymus and activation-regulated chemokine and macrophage-derived chemokine in patients with atopic dermatitis. J Allergy Clin Immunol 2002;110:139–146.
Leavell KJ, Peterson MW, Gross TJ: The role of fibrin degradation products in neutrophil recruitment to the lung. Am J Respir Cell Mol Biol 1996;14:53–60.
Brass LF, Molino M: Protease-activated G protein-coupled receptors on human platelets and endothelial cells. Thromb Haemost 1997;78:234–241.
Miike S, McWilliam AS, Kita H: Trypsin induces activation and inflammatory mediator release from human eosinophils through protease-activated receptor-2. J Immunol 2001;167:6615–6622.
Rasmussen UB, Vouret-Craviari V, Jallat S, Schlesinger Y, Pages G, Pavirani A, Lecocq JP, Pouyssegur J, Obberghen-Schilling E: cDNA cloning and expression of a hamster alpha-thrombin receptor coupled to Ca2+ mobilization. FEBS Lett 1991;288:123–128.
Ishihara H, Connolly AJ, Zeng D, Kahn ML, Zheng YW, Timmons C, Tram T, Coughlin SR: Protease-activated receptor 3 is a second thrombin receptor in humans. Nature 1997;386:502–506.
Xu WF, Andersen H, Whitmore TE, Presnell SR, Yee DP, Ching A, Gilbert T, Davie EW, Foster DC: Cloning and characterization of human protease-activated receptor 4. Proc Natl Acad Sci USA 1998;95:6642–6646.
Hou L, Howells GL, Kapas S, Macey MG: The protease-activated receptors and their cellular expression and function in blood-related cells. Br J Haematol 1998;101:1–9.
Cocks TM, Moffatt JD: Protease-activated receptors: Sentries for inflammation? Trends Pharmacol Sci 2000;21:103–108.
Knight DA, Lim S, Scaffidi AK, Roche N, Chung KF, Stewart GA, Thompson PJ: Protease-activated receptors in human airways: Upregulation of PAR-2 in respiratory epithelium from patients with asthma. J Allergy Clin Immunol 2001;108:797–803.
Cocks TM, Moffatt JD: Protease-activated receptor-2 (PAR2) in the airways. Pulm Pharmacol Ther 2001;14:183–191.
Schmidlin F, Amadesi S, Vidil R, Trevisani M, Martinet N, Caughey G, Tognetto M, Cavallesco G, Mapp C, Geppetti P, Bunnett NW: Expression and function of proteinase-activated receptor 2 in human bronchial smooth muscle. Am J Respir Crit Care Med 2001;164:1276–1281.
Schmidlin F, Amadesi S, Dabbagh K, Lewis DE, Knott P, Bunnett NW, Gater PR, Geppetti P, Bertrand C, Stevens ME: Protease-activated receptor 2 mediates eosinophil infiltration and hyperreactivity in allergic inflammation of the airway. J Immunol 2002;169:5315–5321.
Wardlaw AJ: Molecular basis for selective eosinophil trafficking in asthma: A multistep paradigm. J Allergy Clin Immunol 1999;104:917–926.
Bolton SJ, McNulty CA, Thomas RJ, Hewitt CR, Wardlaw AJ: Expression of and functional responses to protease-activated receptors on human eosinophils. J Leukoc Biol 2003;74:60–68.
Feistritzer C, Sturn DH, Kaneider NC, Djanani A, Wiedermann CJ: Endothelial protein C receptor-dependent inhibition of human eosinophil chemotaxis by protein C. J Allergy Clin Immunol 2003;112:375–381.
He S, Peng Q, Walls AF: Potent induction of a neutrophil and eosinophil-rich infiltrate in vivo by human mast cell tryptase: Selective enhancement of eosinophil recruitment by histamine. J Immunol 1997;159:6216–6225.
Bizios R, Lai L, Fenton JW, Malik AB: Thrombin-induced chemotaxis and aggregation of neutrophils. J Cell Physiol 1986;128:485–490.
Atkins PC, von Allmen C, Moskovitz A, Valenzano M, Zweiman B: Fibrin formation during ongoing cutaneous allergic reactions: Comparison of responses to antigen and codeine. J Allergy Clin Immunol 1993;91:956–960.
Atkins PC, Kaplan AP, von Allmen C, Moskovitz A, Zweiman B: Activation of the coagulation pathway during ongoing allergic cutaneous reactions in humans. J Allergy Clin Immunol 1992;89:552–559.
Gabazza EC, Taguchi O, Tamaki S, Takeya H, Kobayashi H, Yasui H, Kobayashi T, Hataji O, Urano H, Zhou H, Suzuki K, Adachi Y: Thrombin in the airways of asthmatic patients. Lung 1999;177:253–262.
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