Kuna P, Reddigari S R, Schall T J, Rucinski D, Sadick M, Kaplan A P
Department of Medicine, SUNY-Stony Brook, Health Sciences Center 11794-8161.
J Immunol. 1993 Mar 1;150(5):1932-43.
We have tested the histamine releasing properties and priming abilities of a wide range of recombinant or purified cytokines and growth factors on the basophils of 20 subjects (10 atopic and 10 nonatopic). We found that monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1), RANTES, human macrophage inflammatory protein-1 alpha and human inflammatory protein-1 beta, Connective tissue activating peptide III and Neutrophil Activating Peptide-2 (NAP-2) cause histamine release from basophils and are all members of the intercrine/chemokine family. MCAF/MCP-1 was as potent as anti-IgE or C5a and it is clearly the major contributor to histamine releasing factor activity. RANTES was the second major histamine releasing factor among the positive cytokines. Both MCAF/MCP-1 and RANTES are present in conditioned mononuclear cell media and can be separated using Mono Q anion exchange chromatography. We also demonstrated that RANTES has unusual chromatographic properties in spite of its isoelectric point of > 9.0 because it is largely found in peak-2 of the Mono Q column rather than peak-1 in which intercrines such as MCAF/MCP-1, IL-8, and connective tissue activating peptide III are found. All other cytokines and growth factors tested were negative, with the exception of IL-3, which caused histamine release in a subpopulation of subjects, and also primed basophils for release by anti-IgE. Other basophil primers for anti-IgE-dependent histamine release were IL-5, mast cell growth factor (c-kit ligand), and insulin-like growth factor II. Using specific neutralizing antibodies we have shown that MCAF/MCP-1, RANTES, and IL-3 contribute significantly to the activity found in mononuclear cell culture supernatants. Granulocyte-macrophage-CSF, IP-10, I-309, IL-7, IL-8, IL-9, IL-10, IL-11, IgE-binding factor, TNF-alpha, TGF-beta 1, fibroblast growth factor, epidermal growth factor, and endothelial cell growth factor were negative for direct histamine release and as primers of basophils. Our results indicate that cytokines belonging to the intercrine/chemokine family are major constituents of the activity known as "histamine releasing factor" found in MNC supernatants.
我们检测了多种重组或纯化的细胞因子及生长因子对20名受试者（10名特应性个体和10名非特应性个体）嗜碱性粒细胞的组胺释放特性和启动能力。我们发现单核细胞趋化和激活因子/单核细胞趋化蛋白-1（MCAF/MCP-1）、RANTES、人巨噬细胞炎性蛋白-1α和人炎性蛋白-1β、结缔组织激活肽III和中性粒细胞激活肽-2（NAP-2）可引起嗜碱性粒细胞释放组胺，它们均为白细胞介素/趋化因子家族成员。MCAF/MCP-1与抗IgE或C5a的作用相当，显然是组胺释放因子活性的主要贡献者。RANTES是阳性细胞因子中第二大组胺释放因子。MCAF/MCP-1和RANTES均存在于条件性单核细胞培养基中，可用Mono Q阴离子交换色谱法分离。我们还证明，尽管RANTES的等电点>9.0，但它具有不同寻常的色谱特性，因为它主要出现在Mono Q柱的峰2中，而不是出现在发现诸如MCAF/MCP-1、IL-8和结缔组织激活肽III等白细胞介素的峰1中。除IL-3外，所有其他检测的细胞因子和生长因子均为阴性，IL-3可使部分受试者的嗜碱性粒细胞释放组胺，并能启动嗜碱性粒细胞由抗IgE介导的组胺释放。其他可启动抗IgE依赖性组胺释放的嗜碱性粒细胞激活剂有IL-5、肥大细胞生长因子（c-kit配体）和胰岛素样生长因子II。我们使用特异性中和抗体证明，MCAF/MCP-1、RANTES和IL-3对单核细胞培养上清液中的活性有显著贡献。粒细胞-巨噬细胞集落刺激因子、IP-10、I-309、IL-7、IL-8、IL-9、IL-10、IL-11、IgE结合因子、肿瘤坏死因子-α、转化生长因子-β1、成纤维细胞生长因子、表皮生长因子和内皮细胞生长因子在直接组胺释放及作为嗜碱性粒细胞激活剂方面均为阴性。我们的结果表明，属于白细胞介素/趋化因子家族的细胞因子是单核细胞上清液中被称为“组胺释放因子”的活性的主要成分。
