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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
Author(s) -
Majlesi Yasamin,
Samorapoompichit Puchit,
Hauswirth Alexander W.,
Schernthaner GeritHolger,
Ghannadan Minoo,
Baghestanian Mehrdad,
RezaieMajd Abdolreza,
Valenta Rudolf,
Sperr Wolfgang R.,
Bühring HansJörg,
Valent Peter
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0202075
Subject(s) - cerivastatin , atorvastatin , basophil activation , mevalonic acid , basophil , pravastatin , histamine , biology , pharmacology , simvastatin , lovastatin , immunoglobulin e , red yeast rice , immunology , biochemistry , antibody , cholesterol , enzyme , reductase , fermentation
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 3 H‐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.