Adenosine inhibits fMLP-stimulated adherence and superoxide anion generation by human neutrophils at an early step in signal transduction.
Adenosine inhibits fMLP-stimulated adherence and superoxide anion generation by human neutrophils at an early step in signal transduction.
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腺苷在信号转导的早期抑制 fMLP 刺激的粘附和人中性粒细胞产生超氧阴离子。
DOI：
10.1016/0167-4889(93)90223-c
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Webster,RO
中科院分区：
文献类型：
--
作者：
Burkey,TH;Webster,RO
生理浓度的腺苷抑制甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）刺激的超氧阴离子（O− 2）生成、粘附和脱粒的能力在人类中性粒细胞中得到了很好的证实。然而，抑制机制仍有待确定。为了更好地了解腺苷阻断fMLP信号转导途径的位置，我们检查了腺苷抑制由佛波醇肉豆蔻酸酯乙酸酯（PMA）、NaF和A23187刺激的中性粒细胞粘附的能力;这些试剂激活fMLP信号转导的中间步骤。腺苷（0.1-100 μM）不抑制这些受体非依赖性激动剂介导的粘附或NaF和A23187介导的O− 2产生。此外，NaF和A23187完全消除腺苷对fMLP刺激的中性粒细胞粘附的抑制。我们还发现百日咳毒素（5和10 μM）完全抑制fMLP诱导的中性粒细胞粘附和O− 2生成，表明这两个过程都是G蛋白介导的。此外，中性粒细胞膜制备物中fMLP刺激的GTdR活性可被腺苷（1和10 μM）或5′-N-乙基羧酰胺腺苷（1 μM）（NECA）显著抑制。这些数据表明，腺苷抑制G蛋白依赖性途径的fMLP刺激解偶联G蛋白从fMLP受体。这可能是腺苷抑制细胞表面受体介导的信号的一般机制，因为fMLP和C5 a刺激的中性粒细胞粘附在相似浓度下均被抑制。
The ability of physiological concentrations of adenosine to inhibit formylmethionylleucylphenylalanine (fMLP)-stimulated superoxide anion (O− 2) generation, adherence and degranulation is well established in human neutrophils. However, the mechanism of inhibition remains to be determined. To better understand where adenosine blocks the fMLP signal transduction pathway, we examined the ability of adenosine to inhibit neutrophil adherence stimulated by phorbol myristate acetate (PMA), NaF, and A23187; these agents activate intermediate steps in fMLP signal transduction. Adenosine (0.1–100 μM) did not inhibit adherence mediated by these receptor-independent agonists or NaF-and A23187-mediated O− 2 production. Additionally, NaF and A23187 completely abrogated adenosine inhibition of fMLP-stimulated neutrophil adherence. We also found that pertussis toxin (5 and 10 μM) completely inhibited fMLP-induced neutrophil adherence and O− 2 generation, indicating that both processes are G protein mediated. Furthermore, fMLP-stimulated GTPase activity in neutrophil membrane preparations was significantly inhibited by adenosine (1 and 10 μM) or 5′-N-ethylcarboxamidoadenosine (1 μM)(NECA). These data indicate that adenosine inhibits a G-protein-dependent pathway of fMLP stimulation by uncoupling G proteins from the fMLP receptor. This may be a general mechanism of adenosine inhibition of cell-surface receptor-mediated signals as both fMLP-and C5a-stimulated neutrophil adherence were inhibited at similar concentrations.