Davoine Francis, Ferland Claudine, Chakir Jamila, Lee Joo Eun, Adamko Darryl J, Moqbel Redwan, Laviolette Michel
Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Canada.
Int Arch Allergy Immunol. 2006;140(4):277-84. doi: 10.1159/000093705. Epub 2006 May 20.
Animal and human studies demonstrated that interleukin (IL)-12, a Th1 cytokine, reduces blood and bronchial eosinophilia, and airway hyperreactivity. According to current concepts, these effects are mediated through the release of cytokines promoting eosinophil recruitment and activation. However, the presence of IL-12 receptors on eosinophils suggests that IL-12 also acts directly on eosinophils. We postulated that IL-12 directly modulates eosinophil functions and has the capacity to regulate eosinophil degranulation, migration and survival, in vitro.
Effects of IL- 12 on purified human blood eosinophils were evaluated for peroxidase (EPO) release, eotaxin-induced migration through a model of basement membrane (Matrigel), and survival.
IL-12 inhibited 50% of PAF and secretory IgA-induced EPO release (n = 8, p < 0.001). IL-12 also reduced eotaxin-induced migration through Matrigel by 54 +/-6% (n = 6, p < 0.01). These effects were not explained by an IL-12-induced impaired viability or apoptosis.
Our results demonstrate that IL-12 directly modulates eosinophil functions without promoting apoptosis and explain, at least in part, the effects of IL-12 on eosinophils observed in in vivo studies.
动物和人体研究表明，作为一种Th1细胞因子的白细胞介素（IL）-12可减轻血液和支气管嗜酸性粒细胞增多以及气道高反应性。根据目前的概念，这些作用是通过促进嗜酸性粒细胞募集和激活的细胞因子释放来介导的。然而，嗜酸性粒细胞上存在IL-12受体表明IL-12也直接作用于嗜酸性粒细胞。我们推测，IL-12可直接调节嗜酸性粒细胞功能，并在体外具有调节嗜酸性粒细胞脱颗粒、迁移和存活的能力。
通过评估过氧化物酶（EPO）释放、嗜酸性粒细胞趋化因子诱导的穿过基底膜模型（基质胶）的迁移以及存活情况，来研究IL-12对纯化的人血嗜酸性粒细胞的影响。
IL-12抑制了50%的血小板活化因子（PAF）和分泌型IgA诱导的EPO释放（n = 8，p < 0.001）。IL-12还使嗜酸性粒细胞趋化因子诱导的穿过基质胶的迁移减少了54±6%（n = 6，p < 0.01）。这些作用不能用IL-12诱导的活力受损或凋亡来解释。
我们的结果表明，IL-12可直接调节嗜酸性粒细胞功能而不促进凋亡，并且至少部分解释了在体内研究中观察到的IL-12对嗜酸性粒细胞的作用。
