ATP induces transient elevations of [Ca2+]i in human neutrophils and primes these cells for enhanced O2- generation.
ATP induces transient elevations of [Ca2+]i in human neutrophils and primes these cells for enhanced O2- generation.
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ATP 诱导人中性粒细胞中 [Ca2]i 短暂升高，并为这些细胞增强 O2 生成做好准备。
DOI：
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发表时间：
1988
期刊：
影响因子：
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通讯作者：
R. Basford
中科院分区：
文献类型：
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作者：
D. Kuhns;Wright Dg;J. Nath;S. Kaplan;R. Basford
当ATP以与血小板血栓形成部位细胞外获得的浓度（0.1至20 μ M）相似的浓度加入人多形核中性粒细胞（PMN）中时，会导致N-甲酰基（甲硫氨酰基）亮氨酰苯丙氨酸（FMLP）刺激的超氧阴离子（O2-）生成增强。然而，ATP本身是一个无效的激动剂O2-生成的中性粒细胞。ATP诱导的O2-生成增强与PMNs对FMLP的响应中的滞后时间缩短相关，而FMLP的中位有效剂量没有变化，这表明信号转导，而不是改变受体亲和力，是负责增强的氧化反应。最早在15秒时检测到氧气生成的最大增强，并保持至少10分钟。在各种核苷酸和不可水解的ATP类似物试验d中，只有ATP、UTP和ITP被发现引起PMN产生的O2增强。在没有其他刺激的情况下，向quin 2-负载的PMN中添加ATP引起[Ca 2 +]i的急剧上升，其在30秒时达到500至800 nM的最大值，并在5分钟内缓慢返回到基线。这种ATP诱导的细胞内游离Ca 2+浓度的升高与FMLP刺激的O2产生的增强有关，无论是在剂量还是核苷酸特异性方面。刺激的Ca 2+摄取，而不是动员细胞内Ca 2+商店，似乎是主要负责细胞内游离Ca 2+浓度的上升。这些研究表明，ATP诱导的细胞内游离Ca 2+浓度的上升，虽然本身不足以引起O2-生成的中性粒细胞，是与一个引发的中性粒细胞增强O2-生成时，由其他激动剂刺激。
ATP, when added to human polymorphonuclear neutrophils (PMNs) at concentrations similar to those attained extracellularly at sites of platelet thrombus formation (0.1 to 20 microM), causes an enhancement of N-formyl(methionyl)leucylphenylalanine (FMLP)-stimulated superoxide anion (O2-) generation. However, ATP by itself is an ineffective agonist for O2- generation by PMNs. The ATP-induced enhancement of O2- generation is associated with a shortened lag time in the response of PMNs to FMLP without a change in the median effective dose for FMLP, suggesting that signal transduction, rather than altered receptor affinity, is responsible for the enhanced oxidative response. Maximum enhancement of O2- generation is detected as early as 15 seconds and is maintained for at least 10 minutes. Of various nucleotides and nonhydrolyzable-ATP analogs test d, only ATP, UTP, and ITP were found to cause enhanced O2- generation by PMNs. Addition of ATP to quin2-loaded PMNs, in the absence of other stimuli, elicits a dramatic rise in [Ca2+]i which reaches a maximum of 500 to 800 nM at 30 seconds and slowly returns to baseline over 5 minutes. This ATP-induced rise in intracellular free Ca2+ concentration is correlated with the enhancement of FMLP-stimulated O2- generation both with respect to dose and nucleotide specificity. Stimulated Ca2+ uptake, rather than mobilization of intracellular Ca2+ stores, appears to be primarily responsible for the rise in intracellular free Ca2+ concentration. These studies indicate that an ATP-induced rise in intracellular free Ca2+ concentration, although insufficient by itself to elicit O2- generation by PMNs, is associated with a priming of PMNs for enhanced O2- generation when stimulated by other agonists.