Interleukin-3-induced up-regulation of CR3 expression on human eosinophils is inhibited by dexamethasone.
Eosinophil function is regulated by several cytokines, including interleukin-3 (IL-3), IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF). Culture of human eosinophils with IL-3 produced a marked, dose-dependent up-regulation of CR3 expression. This was maximal after 1 day in culture and dependent on protein and RNA synthesis, as demonstrated by inhibition with cycloheximide and actinomycin D, respectively. IL-5 and GM-CSF had a similar effect on eosinophil complement receptor type 3 (CR3) expression, but the maximal response to IL-5 was always less than to IL-3 or GM-CSF. Dexamethasone inhibited the Il-3-induced up-regulation of CR3 expression in a dose-dependent manner, with an IC50 of 5 x 10(-8) M. This study demonstrates the effect of IL-3, IL-5 and GM-CSF on eosinophil CR3 expression and confirms the capacity of eosinophils to modify their phenotype through de novo protein synthesis. This process could be inhibited by physiological concentrations of glucocorticoids, thus providing an additional mechanism for their mode of action in allergic disease.
Hartnell
A
A
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, London, U.K.
Kay
A B
AB
Wardlaw
A J
AJ
D001798:Blood Proteins / Q000096:biosynthesis; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000032:analysis* / Q000187:drug effects
D001798:Blood Proteins; D007377:Interleukin-3; D015848:Interleukin-5; D016177:Macrophage-1 Antigen; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor