Tai P C, Spry C J
Department of Cellular & Molecular Sciences, St George's Hospital Medical School, London, England.
Clin Exp Immunol. 1990 Jun;80(3):426-34. doi: 10.1111/j.1365-2249.1990.tb03305.x.
The effects of recombinant human GM-CSF and interleukin-3 (IL-3) on human blood eosinophil survival, activation, and secretion were studied. Purified normal density eosinophils from patients with the idiopathic hypereosinophilic syndrome (HES) survived in culture for 7 days (50% viable) in the presence of 50 nM GM-CSF or 50 nM IL-3. Neutrophils did not survive after 4 days. No eosinophils survived in the absence of GM-CSF or IL-3. In two out of five patients studied, the cultured eosinophils became elongated with numerous processes. In all five patients the cells became adherent, but there were no morphological signs of degranulation. Both GM-CSF and IL-3 activated eosinophils, transforming the storage form of eosinophil cationic protein (ECP) into the secreted form. The proportion of activated cells increased from less than 20% to over 50% after 4 days in culture. However, GM-CSF and IL-3 did not induce secretion on their own. On the other hand, when GM-CSF/IL-3-activated eosinophils were exposed to known secretory stimuli, there was a six-fold increase in the amount of ECP released when the cells were stimulated with sepharose coated with C3b, and a two-fold increase when they were stimulated with sepharose-activated whole autologous serum. Eosinophils from patients taking steroids were unable to secrete their granule contents, even though they became activated by GM-CSF and IL-3. A novel finding was that sepharose-activated whole serum was an extremely potent secretory signal for ECP, releasing up to 50% of the total ECP content. These studies showed that GM-CSF and IL-3 prime eosinophil effector function by initiating granule solubilization which is the first step in the secretory event, without affecting the subsequent extracellular release of granule proteins.
研究了重组人粒细胞巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-3（IL-3）对人血嗜酸性粒细胞存活、活化及分泌的影响。来自特发性嗜酸性粒细胞增多综合征（HES）患者的纯化正常密度嗜酸性粒细胞，在存在50 nM GM-CSF或50 nM IL-3的情况下，可在培养中存活7天（50%存活）。中性粒细胞在4天后无法存活。在没有GM-CSF或IL-3的情况下，没有嗜酸性粒细胞存活。在研究的5名患者中有2名，培养的嗜酸性粒细胞变得细长并带有许多突起。在所有5名患者中，细胞都变得贴壁，但没有脱颗粒的形态学迹象。GM-CSF和IL-3均能激活嗜酸性粒细胞，将嗜酸性粒细胞阳离子蛋白（ECP）的储存形式转化为分泌形式。培养4天后，活化细胞的比例从不到20%增加到超过50%。然而，GM-CSF和IL-3自身并不诱导分泌。另一方面，当GM-CSF/IL-3激活的嗜酸性粒细胞暴露于已知的分泌刺激时，用包被有C3b的琼脂糖刺激细胞时，释放的ECP量增加了6倍，用琼脂糖激活的全自体血清刺激时，释放量增加了2倍。服用类固醇的患者的嗜酸性粒细胞即使被GM-CSF和IL-3激活，也无法分泌其颗粒内容物。一个新发现是，琼脂糖激活的全血清是ECP的一种极其有效的分泌信号，可释放高达总ECP含量的50%。这些研究表明，GM-CSF和IL-3通过启动颗粒溶解来引发嗜酸性粒细胞效应功能，颗粒溶解是分泌事件的第一步，而不影响随后颗粒蛋白的细胞外释放。
