Adenosine triphosphate-induced oxygen radical production and CD11b up-regulation:: Ca++ mobilization and actin reorganization in human eosinophils
Adenosine triphosphate-induced oxygen radical production and CD11b up-regulation:: Ca++ mobilization and actin reorganization in human eosinophils
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DOI：
10.1182/blood.v95.3.973.003k47_973_978
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发表时间：
2000-02-01
期刊：
影响因子：
20.3
通讯作者：
Norgauer, J
中科院分区：
文献类型：
--
作者：
Dichmann, S;Idzko, M;Norgauer, J
嗜酸性粒细胞是细胞炎症如寄生虫感染、特应性疾病、大疱性皮肤病和血管炎中的主要效应细胞。三磷酸腺苷（ATP）在人嗜酸性粒细胞中的生物学活性被表征，并与其它嗜酸性粒细胞活化剂如补体片段产物C5 a、血小板活化因子（PAF）和嗜酸性粒细胞活化趋化因子（eotaxin）的生物学活性进行比较，ATP启动活性氧代谢产物的产生，如光泽精依赖性化学发光所证明的。此外，ATP引起整合素CD 11b的上调。此外，荧光显微镜测量标记的Fura-2（1-[2-（5-羧基-恶唑-2-基）-6-氨基苯并呋喃-5-氧基]-2-（三氟甲基）苯并呋喃（2 '-氨基-5'-甲基-苯氧基）乙烷N，N，N，N '-四乙酸，在存在或不存在乙二醇四乙酸（EGTA）的情况下，五乙酰氧基甲基酯）嗜酸性粒细胞表明有Ca++流式细胞术研究表明，在ATP及其稳定的类似物腺苷5 '-0-（3-硫代三磷酸）和2-甲硫基腺苷三磷酸四磷酸（met-ATP），ATP诱导的反应与C5 a、PAF和嗜酸性粒细胞趋化因子获得的反应相当，百日咳毒素可抑制ATP刺激后活性氧代谢产物的产生和肌动蛋白的聚合，这表明受体偶联的鸟嘌呤核苷酸结合蛋白（G（i）蛋白）的参与。此外，氧化ATP的实验也表明P2 X受体参与了这一激活过程。结果表明，ATP是嗜酸性粒细胞的强激活剂，具有与嗜酸性粒细胞趋化因子C5 a、PAF和嗜酸性粒细胞趋化因子相当的生物活性。(C)2000年，美国血液学会。
Eosinophils are major effector cells in cellular inflammatory conditions such as parasitic infections, atopic diseases, bullous dermatoses, and vasculitis, Biological activities of adenosine triphosphate (ATP) were characterized in human eosinophils and compared with those of other eosinophil activators such as complement fragment product C5a, platelet-activating factor (PAF), and eotaxin, ATP initiated production of reactive oxygen metabolites, as demonstrated by lucigenin-dependent chemiluminescence. Furthermore, ATP caused up-regulation of the integrin CD11b, In addition, fluorescence microscope measurements labeled with fura-2 (1-[2-(5-carboxy-oxazol-2-yl)-6-aminobenzofuran-5-oxy]-2-(2'-amino-5'-methyl-phenoxy)ethaneN, N, N, N'-tetraacetic acid, pentaacetoxymethyl ester) eosinophils in the presence or absence of ethyleneglycotetraacetic acid (EGTA) indicated that there was Ca++ mobilization from intracellular stores by ATP, Flow cytometric studies showed transient actin polymerization upon stimulation with ATP and its stable analogues adenosine 5'-0-(3-thiotriphosphate) and 2-methylthioadenosine triphosphate tetrasodium (met-ATP), The reactions induced by ATP were comparable to those obtained by C5a, PAF and eotaxin, Production of reactive oxygen metabolites and actin polymerization after stimulation with ATP was inhibited by pertussis toxin, which indicated involvement of receptor-coupled guanine nucleotide-binding proteins (G(i) proteins). In addition, experiments with oxidized ATP also suggest involvement of P2X receptors in this activation process, The results show that ATP is a strong activator of eosinophils and has biological activity comparable to those of the eosinophil chemotaxins C5a, PAF, and eotaxin, The findings strongly suggest a role of ATP in the pathogenesis of eosinophilic inflammation as an activator of proinflammatory effector functions.(C) 2000 by The American Society of Hematology.