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.
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 microM) 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 microM). 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.
Majlesi
Yasamin
Y
Department of Internal Medicine I, Division of Hematology & Hemostaseology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Samorapoompichit
Puchit
P
Hauswirth
Alexander W
AW
Schernthaner
Gerit-Holger
GH
Ghannadan
Minoo
M
Baghestanian
Mehrdad
M
Rezaie-Majd
Abdolreza
A
Valenta
Rudolf
R
Sperr
Wolfgang R
WR
Bühring
Hans-Jörg
HJ
Valent
Peter
P
D015703:Antigens, CD / Q000032:analysis; D000069059:Atorvastatin; D001491:Basophils / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007377:Interleukin-3 / Q000502:physiology; D010727:Phosphoric Diester Hydrolases / Q000096:biosynthesis / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D011755:Pyrophosphatases / Q000096:biosynthesis / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*
D015703:Antigens, CD; C427944:ENPP3 protein, human; D006538:Heptanoic Acids; D007377:Interleukin-3; D011725:Pyridines; D011758:Pyrroles; D007073:Immunoglobulin E; D000069059:Atorvastatin; C086276:cerivastatin; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases