Cromwell O, Moqbel R, Fitzharris P, Kurlak L, Harvey C, Walsh G M, Shaw R J, Kay A B
Department of Allergy and Clinical Immunology, Cardiothoracic Institute, London, England.
J Allergy Clin Immunol. 1988 Oct;82(4):535-43. doi: 10.1016/0091-6749(88)90962-1.
Sepharose beads coated with IgG stimulate eosinophils to produce leukotriene C4 (LTC4). This observation has been extended with specific immobilized IgG/antigen immune complexes to elicit mediator generation. An extract of Aspergillus fumigatus was covalently coupled to Sepharose beads and incubated with the IgG fraction of immune serum from patients with allergic bronchopulmonary aspergillosis. These beads elicited generation of 7.72 +/- 1.7 pmol of LTC4 immunoreactive material (n = 5) from 1 X 10(6) normal eosinophils of greater than 86% purity, and significantly less LTC4 (0.73 +/- 0.19 pmol per 10(6) cells; n = 3) was produced by eosinophils after incubation with beads treated with IgG from normal nonimmune serum. The maximum antibody-dependent release achieved represented approximately 20% of that induced by the calcium ionophore (A23187). LTC4 was measured by radioimmunoassay and validated by reverse-phase high-performance liquid chromatography. The amount of LTC4 generated was dependent on the concentration of A. fumigatus-specific IgG, and mediator release was completely abolished by prior adsorption of the IgG fraction onto Sepharose-protein A (Staphylococcus aureus). Grass pollen-specific IgG antibody/antigen complexes, in combination with Sepharose beads, also triggered generation of LTC4 immunoreactive material. There was no evidence to suggest that IgE/A. fumigatus immune complexes triggered LTC4 generation, although IgE myeloma protein, in association with Sepharose beads, was a weak stimulus. The efficacy of the IgG immune complex-dependent stimulation of eosinophils suggests a possible physiologic mechanism whereby these cells could participate in the inflammatory changes associated with allergic bronchopulmonary aspergillosis and similar allergic disorders.
包被有IgG的琼脂糖珠可刺激嗜酸性粒细胞产生白三烯C4（LTC4）。这一观察结果已通过特异性固定化IgG/抗原免疫复合物得以扩展，以引发介质生成。烟曲霉菌提取物与琼脂糖珠共价偶联，并与过敏性支气管肺曲霉菌病患者免疫血清的IgG组分一起孵育。这些珠子可从1×10⁶个纯度大于86%的正常嗜酸性粒细胞中引发7.72±1.7皮摩尔的LTC4免疫反应性物质生成（n = 5），而与来自正常非免疫血清的IgG处理过的珠子孵育后的嗜酸性粒细胞产生的LTC4明显较少（每10⁶个细胞0.73±0.19皮摩尔；n = 3）。所实现的最大抗体依赖性释放约占钙离子载体（A23187）诱导释放量的20%。LTC4通过放射免疫测定法进行测量，并通过反相高效液相色谱法进行验证。所生成的LTC4量取决于烟曲霉菌特异性IgG的浓度，并且通过事先将IgG组分吸附到琼脂糖-蛋白A（金黄色葡萄球菌）上，介质释放完全被消除。草花粉特异性IgG抗体/抗原复合物与琼脂糖珠结合，也能触发LTC4免疫反应性物质的生成。没有证据表明IgE/烟曲霉菌免疫复合物能触发LTC4生成，尽管IgE骨髓瘤蛋白与琼脂糖珠结合是一种较弱的刺激。IgG免疫复合物对嗜酸性粒细胞的依赖性刺激作用表明了一种可能的生理机制，通过该机制这些细胞可能参与与过敏性支气管肺曲霉菌病及类似过敏性疾病相关的炎症变化。
