Alam R, Forsythe P, Stafford S, Heinrich J, Bravo R, Proost P, Van Damme J
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555.
J Immunol. 1994 Oct 1;153(7):3155-9.
Cytokine-dependent mediator release from basophils and mast cells may play an important role in the pathogenesis of allergic and inflammatory conditions. Many C-C chemokines have been found to activate basophils and mast cells. We investigated the effect of three newly identified C-C chemokines, monocyte chemotactic protein-2 and -3 (MCP-2, MCP-3) and fibroblast-induced cytokine (FIC) on basophils and mast cells. We found that all three cytokines induced histamine secretion from basophils in a dose-dependent manner. The secretion of histamine was a Ca(2+)-dependent process. MCP-3 was the most potent activator of basophils. MCP-3 and FIC activated basophils from all study subjects, whereas the histamine release by MCP-2 was donor-dependent. The histamine-releasing activity of MCP-2, MCP-3, and FIC was compared with that of MCP-1, RANTES, and macrophage inflammatory protein-1 alpha using basophils from 10 donors. MCP-1 was the most potent among all the C-C chemokines. However, MCP-3 was nearly as potent. MCP-2, MCP-3, and FIC induced significant chemotaxis of basophils. None of the cytokines activated mouse peritoneal mast cells. The synthesis of mRNA for MCP-3 was investigated by reverse-transcription PCR using allergen-stimulated PBMC and bronchoalveolar lavage cells. Both MNC and bronchoalveolar lavage cells expressed mRNA for MCP-3. The results of this study indicate that MCP-2, MCP-3, and FIC are novel histamine-releasing factors.
细胞因子依赖性介质从嗜碱性粒细胞和肥大细胞的释放可能在过敏性和炎症性疾病的发病机制中起重要作用。许多C-C趋化因子已被发现可激活嗜碱性粒细胞和肥大细胞。我们研究了三种新发现的C-C趋化因子，单核细胞趋化蛋白-2和-3（MCP-2、MCP-3）和成纤维细胞诱导细胞因子（FIC）对嗜碱性粒细胞和肥大细胞的影响。我们发现所有这三种细胞因子均以剂量依赖性方式诱导嗜碱性粒细胞分泌组胺。组胺的分泌是一个依赖Ca(2+)的过程。MCP-3是嗜碱性粒细胞最有效的激活剂。MCP-3和FIC激活了所有研究对象的嗜碱性粒细胞，而MCP-2引起的组胺释放则依赖于供体。使用来自10名供体的嗜碱性粒细胞，将MCP-2、MCP-3和FIC的组胺释放活性与MCP-1、RANTES和巨噬细胞炎性蛋白-1α的组胺释放活性进行了比较。MCP-1在所有C-C趋化因子中最有效。然而，MCP-3的效力几乎与之相同。MCP-2、MCP-3和FIC诱导嗜碱性粒细胞产生显著的趋化作用。这些细胞因子均未激活小鼠腹膜肥大细胞。使用变应原刺激的外周血单核细胞（PBMC）和支气管肺泡灌洗细胞，通过逆转录聚合酶链反应（RT-PCR）研究了MCP-3的mRNA合成。单核细胞（MNC）和支气管肺泡灌洗细胞均表达MCP-3的mRNA。本研究结果表明，MCP-2、MCP-3和FIC是新型组胺释放因子。
