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(Journal of Leukocyte Biology. 2003;73:107-117.)
© 2003 by Society for Leukocyte Biology

Cerivastatin and atorvastatin inhibit IL-3-dependent differentiation and IgE-mediated histamine release in human basophils and downmodulate expression of the basophil-activation antigen CD203c/E-NPP3

Yasamin Majlesi^*, Puchit Samorapoompichit, Alexander W. Hauswirth^*, Gerit-Holger Schernthaner^*,, Minoo Ghannadan^*, Mehrdad Baghestanian, Abdolreza Rezaie-Majd, Rudolf Valenta, Wolfgang R. Sperr^*, Hans-Jörg Bühring^¶ and Peter Valent^*

^* Departments of Internal Medicine I, Division of Hematology & Hemostaseology,
Internal Medicine II, Division of Angiology, and
Pathophysiology, and
Institute of Histology & Embryology, University of Vienna, Austria; and
^¶ Department of Internal Medicine II, University of Tübingen, Germany

Correspondence: Peter Valent, M.D., Department of Internal Medicine I, Division of Hematology & Hemostaseology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. E-mail: peter.valent{at}akh-wien.ac.at

Recent data suggest that the statins, apart from their lipid-lowering activity, exhibit profound anti-inflammatory effects. Basophils are major proinflammatory effector cells in diverse pathologic reactions. We have examined the in vitro effects of five different statins on primary human basophils, their progenitors, and the basophil cell line KU-812. Preincubation of blood basophils with cerivastatin or atorvastatin (0.1–100 µM) for 24 h reduced their capacity to release histamine on immunoglobulin E (IgE)-dependent stimulation in a dose-dependent manner. These statins also inhibited IgE-dependent up-regulation of the basophil-activation antigen CD203c. Moreover, both statins suppressed interleukin-3-induced differentiation of basophils from their progenitors as well as ³H-thymidine uptake in KU-812 cells. All inhibitory effects of cerivastatin and atorvastatin were reversed by mevalonic acid (200 µM). The other statins tested (lovastatin, simvastatin, pravastatin) did not show significant inhibitory effects on basophils. Together, these data identify cerivastatin and atorvastatin as novel inhibitors of growth and activation of human basophils.

Key Words: IgE receptor • allergy • CD203c • progenitor cells

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