Redrup A C, Howard B P, MacGlashan D W, Kagey-Sobotka A, Lichtenstein L M, Schroeder J T
The Johns Hopkins University School of Medicine, Division of Clinical Immunology, Baltimore, MD 21224, USA.
J Immunol. 1998 Feb 15;160(4):1957-64.
Human basophils are an important source of IL-4, a cytokine that is central to the pathogenesis of allergic inflammation. Recent reports have indicated that these cells also generate IL-13, which shares a number of biologic properties with IL-4. We found basophils to be the major source of IL-13 produced in mixed leukocyte cultures following 20-h activation with a variety of stimuli. While the magnitude of IL-4 protein generated correlated with the percent histamine secreted (r = 0.8; p = 0.007), there was no relationship between the levels of IL-13 detected and the amount of either IL-4 or histamine in cultures activated with IL-3/anti-IgE. The induction of IL-13 secretion also occurred in response to IL-3 alone, without concomitant secretion of either IL-4 or histamine. Although previously shown to inhibit IL-4 secretion, the phorbol ester PMA was a potent stimulus for IL-13 generation from basophils, and this secretion was sensitive to the protein kinase C inhibitor, bisindolylmaleimide. In contrast, bisindolylmaleimide did not prevent cytokine secretion induced by either anti-IgE or IL-3. The immunosuppressant, FK506, while strikingly inhibiting the accumulation of IL-4 mRNA and the secretion of protein in response to IL-3/anti-IgE, had no effect on the generation of IL-13 in these cultures; the resistance was attributed to the IL-3-dependent signaling. Similarly, FK506 had no effect on the secretion of IL-13 in basophil cultures stimulated with PMA. This study suggests that multiple intracellular mechanisms control the generation of IL-13 in basophils, some of which are distinct from those regulating IL-4.
人嗜碱性粒细胞是白细胞介素-4（IL-4）的重要来源，IL-4是一种在过敏性炎症发病机制中起核心作用的细胞因子。最近的报告表明，这些细胞还能产生IL-13，IL-13与IL-4具有许多生物学特性。我们发现，在用多种刺激物激活20小时后的混合白细胞培养物中，嗜碱性粒细胞是产生IL-13的主要来源。虽然产生的IL-4蛋白量与分泌的组胺百分比相关（r = 0.8；p = 0.007），但在用IL-3/抗IgE激活的培养物中，检测到的IL-13水平与IL-4或组胺的量之间没有关系。单独用IL-3刺激也会诱导IL-13分泌，且不会伴随IL-4或组胺的分泌。虽然佛波酯PMA以前被证明可抑制IL-4分泌，但它是嗜碱性粒细胞产生IL-13的有效刺激物，且这种分泌对蛋白激酶C抑制剂双吲哚马来酰胺敏感。相比之下，双吲哚马来酰胺并不能阻止抗IgE或IL-3诱导的细胞因子分泌。免疫抑制剂FK506虽然能显著抑制IL-3/抗IgE刺激后IL-4 mRNA的积累和蛋白分泌，但对这些培养物中IL-13的产生没有影响；这种抗性归因于IL-3依赖性信号传导。同样，FK506对PMA刺激的嗜碱性粒细胞培养物中IL-13的分泌也没有影响。这项研究表明，多种细胞内机制控制嗜碱性粒细胞中IL-13的产生，其中一些机制与调节IL-4的机制不同。
