Nilsson G, Johnell M, Hammer C H, Tiffany H L, Nilsson K, Metcalfe D D, Siegbahn A, Murphy P M
Department of Pathology, University Hospital, University of Uppsala, Sweden.
J Immunol. 1996 Aug 15;157(4):1693-8.
Mast cells are known to accumulate at sites of inflammation, however, the chemotaxins involved are undefined. Since most natural leukocyte secretagogues also induce cell migration, and since the anaphylatoxins C3a and C5a are mast cell secretagogues, we hypothesized that both C3a and C5a are also mast cell chemotaxins. Here we report that C3a and C5a are, in fact, potent chemotaxins for the human mast cell line HMC-1. The optimal concentrations, half-maximal effective concentrations (a measure of agonist potency) and the efficacy (response at the optimal concentration) compared with medium control were, for C3a: 10 nM, 0.5 nM, and 256%, respectively; for C5a: 1 nM, 10 pM and 145%. Chemotaxis of HMC-1 cells to both C3a and C5a was blocked by pertussis toxin, suggesting that Gi-coupled receptors are involved in signal transduction. C3a and C5a also induced transient pertussis toxin-inhibitable increases in [Ca2+]i (ED50 = 1 nM for both) that could be homologously but not heterologously desensitized, suggesting that the receptors for C3a and C5a are distinct. These results make C3a the most effective mast cell chemotaxin identified to date. The chemotactic potency described here for C3a is also 100- to 1000-fold greater than for all of its previously described cellular actions. Direct chemoattraction of mast cells by C3a and C5a may help explain the rapid accumulation of mast cells at sites of inflammation.
已知肥大细胞会在炎症部位聚集，然而，其中涉及的趋化因子尚不清楚。由于大多数天然白细胞分泌刺激剂也会诱导细胞迁移，并且过敏毒素C3a和C5a是肥大细胞分泌刺激剂，我们推测C3a和C5a也是肥大细胞趋化因子。在此我们报告，事实上，C3a和C5a是人类肥大细胞系HMC-1的有效趋化因子。与培养基对照相比，C3a的最佳浓度、半数最大效应浓度（一种激动剂效力的衡量指标）和效力（最佳浓度下的反应）分别为：10 nM、0.5 nM和256%；C5a的分别为：1 nM、10 pM和145%。百日咳毒素可阻断HMC-1细胞对C3a和C5a的趋化作用，这表明Gi偶联受体参与信号转导。C3a和C5a还诱导了[Ca2+]i的短暂百日咳毒素抑制性增加（两者的半数有效剂量均为1 nM），这种增加可被同源脱敏但不能被异源脱敏，这表明C3a和C5a的受体是不同的。这些结果使C3a成为迄今为止鉴定出的最有效的肥大细胞趋化因子。此处描述的C3a的趋化效力也比其先前描述的所有细胞作用的效力大100至1000倍。C3a和C5a对肥大细胞的直接化学吸引可能有助于解释肥大细胞在炎症部位的快速聚集。
