Valent P, Schmidt G, Besemer J, Mayer P, Zenke G, Liehl E, Hinterberger W, Lechner K, Maurer D, Bettelheim P
I. Medical Department, University of Vienna, Austria.
Blood. 1989 May 15;73(7):1763-9.
The effect of recombinant human (rh) cytokines, interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL-4), granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), monocyte/macrophage colony stimulating factor (M-CSF), interferon-alpha (IF-alpha), interferon-gamma (IF-gamma), and the tumor necrosis factor-alpha (TNF-alpha) on differentiation and function of metachromatic cells (MCS) was studied. Among all cytokines tested, rh interleukin-3 (rhIL-3) selectively induced a significant formation of MCS (IL-3: 1.1 +/- 0.6 x 10(5) v control: 0.02 +/- 0.15 x 10(5) MCS/mL suspension) and dose dependent increase in formation of intracellular histamine (IL-3, 100 U/mL: 95 +/- 23 ng/mL v control: 1.8 +/- 0.8 ng/mL) in a bone marrow suspension culture system (analyzed on day 14 of culture). Besides MCS, formation of eosinophils was observed in this culture system in the continuous presence of rhIL-3, whereas IL-3 pulse-stimulation for three hours and subsequent exposure to control medium induced growth of MCS but not of eosinophils. By combined immunofluorescence/toluidine blue staining, MCS were found to express a cell surface marker profile that corresponds to the immunological phenotype of peripheral blood basophils (MY-7(CD13)+, VIM12(CD11b)+, VIM2+, MAX1-, MAX24- and YB5B8-). Furthermore, cultured MCS expressed surface membrane receptors for IgE and could be triggered for nontoxic histamine release by a monoclonal anti-IgE antibody. To evaluate a possible influence of IL-3 on basophil function, studies were extended to freshly obtained blood basophils (healthy volunteers, n = 3). However, like all other cytokines tested, rhIL-3 failed to induce basophil histamine release. Taken together, our studies demonstrate that IL-3 is a differentiation factor for human basophils.
研究了重组人(rh)细胞因子,即白细胞介素-1α(IL-1α)、白细胞介素-2(IL-2)、白细胞介素-3(IL-3)、白细胞介素-4(IL-4)、粒细胞/巨噬细胞集落刺激因子(GM-CSF)、粒细胞集落刺激因子(G-CSF)、单核细胞/巨噬细胞集落刺激因子(M-CSF)、干扰素-α(IF-α)、干扰素-γ(IF-γ)以及肿瘤坏死因子-α(TNF-α)对异染性细胞(MCS)分化和功能的影响。在所有测试的细胞因子中,rh白细胞介素-3(rhIL-3)能选择性地显著诱导MCS形成(IL-3:1.1±0.6×10⁵对对照组:0.02±0.15×10⁵个MCS/毫升悬浮液),并在骨髓悬浮培养系统中(在培养第14天分析)使细胞内组胺形成呈剂量依赖性增加(IL-3,100 U/毫升:95±23纳克/毫升对对照组:1.8±0.8纳克/毫升)。除了MCS,在rhIL-3持续存在的情况下,此培养系统中还观察到嗜酸性粒细胞的形成,而用IL-3脉冲刺激三小时后再置于对照培养基中,则诱导了MCS的生长,但未诱导嗜酸性粒细胞的生长。通过联合免疫荧光/甲苯胺蓝染色发现,MCS表达的细胞表面标志物谱与外周血嗜碱性粒细胞的免疫表型相符(MY-7(CD13)+、VIM12(CD11b)+、VIM2+、MAX1-、MAX24-和YB5B8-)。此外,培养的MCS表达IgE的表面膜受体,并且可被单克隆抗IgE抗体触发释放无毒组胺。为评估IL-3对嗜碱性粒细胞功能的可能影响,研究扩展至新鲜获取的血液嗜碱性粒细胞(健康志愿者,n = 3)。然而,与所有其他测试的细胞因子一样,rhIL-3未能诱导嗜碱性粒细胞释放组胺。综上所述,我们的研究表明IL-3是人类嗜碱性粒细胞的分化因子。