Thrombin affects eosinophil migration via protease-activated receptor-1.
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.
Division of General Internal Medicine, Department of Internal Medicine, Medical University of Innsbruck, Anichstrasse 35, AT-6020 Innsbruck, Austria.
Clemens
C
Feistritzer
Birgit A
BA
Mosheimer
Nicole C
NC
Kaneider
Matthias
M
Riewald
Josef R
JR
Patsch
Christian J
CJ
Wiedermann
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D044463:Receptor, PAR-1 / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000819:agonists; D013917:Thrombin / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D013917:Thrombin