Hartnell A, Kay A B, Wardlaw A J
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, London, U.K.
Immunology. 1992 Dec;77(4):488-93.
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.
嗜酸性粒细胞的功能受多种细胞因子调节,包括白细胞介素-3(IL-3)、IL-5和粒细胞-巨噬细胞集落刺激因子(GM-CSF)。用人嗜酸性粒细胞与IL-3培养可使CR3表达产生显著的剂量依赖性上调。培养1天后这种上调达到最大值,且分别通过放线菌酮和放线菌素D抑制证明其依赖于蛋白质和RNA合成。IL-5和GM-CSF对嗜酸性粒细胞补体受体3(CR3)表达有类似作用,但对IL-5的最大反应始终小于对IL-3或GM-CSF的反应。地塞米松以剂量依赖性方式抑制IL-3诱导的CR3表达上调,IC50为5×10⁻⁸M。本研究证明了IL-3、IL-5和GM-CSF对嗜酸性粒细胞CR3表达的影响,并证实了嗜酸性粒细胞通过从头合成蛋白质来改变其表型的能力。这一过程可被生理浓度的糖皮质激素抑制,从而为其在过敏性疾病中的作用方式提供了一种额外机制。