Hirai K, Miyamasu M, Yamaguchi M, Nakajima K, Ohtoshi T, Koshino T, Takaishi T, Morita Y, Ito K
Department of Medicine and Physical Therapy, University of Tokyo, School of Medicine, Japan.
J Immunol. 1993 Feb 15;150(4):1503-8.
Several lines of evidence indicate that basophils play an active pathogenic role in the late-phase reaction. Inasmuch as various cytokines are produced locally by activated cells of the immune system during late-phase reaction, "priming" of basophils by cytokines has become an area of active study over the last few years. We studied the effect of insulin-like growth factor (IGF)-I, shown to be active on immature and mature hemopoietic cells, on histamine release from human basophils. IGF-I enhanced histamine release initiated by anti-IgE, calcium ionophore A23187, and phorbol ester in a dose-dependent fashion (ED50: 300-600 pM), although IGF-I had little or no effect on the release caused by FMLP and C5a. The priming effect of IGF-I took place rapidly and reached plateau levels in 15 min. IGF-II and insulin, both of which have high amino acid sequence homology with IGF-I, also primed basophils. The order of enhancing potencies was IGF-I > IGF-II > insulin; IGF-I was 10-fold more potent than IGF-II and 250-fold more potent than insulin. Although specific receptors for each factor have been identified, blocking experiments using a mAb against IGF-I receptor showed almost complete abolishment of the enhancing effect of these factors, indicating that the enhancing effect is exhibited via the IGF-I receptor. Inasmuch as IGF-I has been shown to be produced by alveolar macrophages, fibroblasts, and nasal polyps, these results indicate that IGF may regulate allergic reactions in vivo by enhancing histamine release from basophils.
多条证据表明嗜碱性粒细胞在迟发相反应中发挥着积极的致病作用。由于在迟发相反应期间免疫系统的活化细胞会在局部产生多种细胞因子，因此细胞因子对嗜碱性粒细胞的“致敏”在过去几年中已成为一个活跃的研究领域。我们研究了胰岛素样生长因子（IGF）-I对人嗜碱性粒细胞组胺释放的影响，IGF-I已被证明对未成熟和成熟造血细胞有活性。IGF-I以剂量依赖性方式增强由抗IgE、钙离子载体A23187和佛波酯引发的组胺释放（半数有效剂量：300 - 600 pM），尽管IGF-I对FMLP和C5a引起的释放几乎没有影响。IGF-I的致敏作用迅速发生，并在15分钟内达到平台水平。与IGF-I具有高氨基酸序列同源性的IGF-II和胰岛素也能使嗜碱性粒细胞致敏。增强效力的顺序为IGF-I > IGF-II > 胰岛素；IGF-I的效力比IGF-II高10倍，比胰岛素高250倍。尽管已鉴定出每种因子的特异性受体，但使用抗IGF-I受体的单克隆抗体进行的阻断实验表明，这些因子的增强作用几乎完全被消除，这表明增强作用是通过IGF-I受体表现出来的。由于已证明肺泡巨噬细胞、成纤维细胞和鼻息肉可产生IGF-I，这些结果表明IGF可能通过增强嗜碱性粒细胞的组胺释放来调节体内的过敏反应。
