ATP对中性粒细胞H_2O_2产生双重作用机制的研究

THE MECHANISMS OF THE BIPHASIC EFFECTS OF ATP ON H2O2 PRODUCTION IN HUMAN NEUTROPHTLS

本文通过高压液相法测定ATP的代谢,探讨其对中性粒细胞H_2O_2产生双重作用的机制。结果显示,ATP本身不能激活中性粒细胞产生H_2O_2,但却对fMLP活化的中性粒细胞有双重作用。ATP与中性粒细胞水浴2min,H_2O_2产生明显增加,当水浴时间延长至5min时,H_2O_2的产生明显受抑制。这种变化在时间上恰好与ATP的代谢一致。ATP从2min开始迅速转为ADP和AMP,AMP又进一步水解为腺苷。ATP对白细胞的抑制作用能被腺苷受体拮抗剂CGS15943抵消。表明ATP对白细胞的双重作用,即开始的兴奋继之抑制与其代谢形成腺苷有关。换句话说,ATP对白细胞的兴奋作用是通过ATP的P_(2u)受体,而抑制作用是通过腺苷A_2受体。

Metabolism of ATP was studied by HPLC assay in order to elucidate the mechanism of the biphasic effects of ATP on H2O2 production by fMLP(formyl-methionyl-leucyl-phenylalanine)-stimulated neutrophils. Results show that ATP was found to be ineffective per se on H2O2 production as a stimulus, but there were biphasic effects on fMLP-stimulated neutrophils. ATP and neutrophils were incubated for 2 min, H2O2 production was increased markedly. With the prolong of time at 5 min, H2O2 production was changed into inhibition. This change is coincided with metabolisn of ATP in time course. ATP starting from 2 min was changed into ADP and AMP, which was breakdowned to adenosine. The inhibition of ATP on neutrophils was antagonized by CGS15943, an antagonist of adenosine. It was indicated that the biphasic effects of ATP, from stimulation to inhibition,was related to metabolism of ATP to adenosine. In other words, the stimulation was performed by P2ureceptor, while the inhibition was performed by adenosine A2 receptor.