Impaired surface expression of PAF receptors on human neutrophils is dependent upon cell activation.
Impaired surface expression of PAF receptors on human neutrophils is dependent upon cell activation.
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人中性粒细胞上 PAF 受体表面表达受损取决于细胞激活。
DOI：
10.1006/abbi.1994.1062
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发表时间：
1994
影响因子：
3.9
通讯作者：
Olson,MS
中科院分区：
文献类型：
--
作者：
Zhou,W;Javors,MA;Olson,MS
人中性粒细胞结合PAF的能力在生理激动剂(N-甲硫基亮氨酸苯丙氨酸(FMLP)、白三烯B4(LTB4))和药理激动剂(佛波醇12-肉豆蔻酸13-乙酸酯(PMA)，A23187)刺激下迅速减弱。因此，中性粒细胞的PAF反应被钝化，这是通过抑制细胞内钙动员来监测的。不同的激动剂对中性粒细胞PAF受体的下调是温度敏感的，需要完整的细胞。结合数据的Scatchard分析显示，PAF结合位点丢失，而配体与受体的亲和力没有明显变化。PAF受体拮抗剂WEB2086与中性粒细胞的结合与PAF结合同时减少。PMA诱导的PAF受体下调对耳孢菌素敏感，而A23187、FMLP或LTB诱导的PAF受体下调对星形孢子素耐药。中性粒细胞聚集(细胞间黏附的一种形式)和PAF受体下调仅在高浓度激动剂时发生，而其他信号过程，如[Ca2+]i增加、PKC激活和PAF合成在低浓度激动剂时被刺激。此外，只有在激活的中性粒细胞被搅拌(或摇动)并允许聚集的条件下，才能观察到激动剂诱导的PAF受体下调。此外，细胞外Ca~(2+)与EGTA的螯合使细胞聚集最小化，也抑制了PAF受体的下调。虽然生化信号的性质或质膜中与聚集相关或随后聚集的物理变化仍有待阐明，但很明显，细胞激活(即中性粒细胞聚集)的充分表达是PAF受体下调所必需的。
The capacity of human neutrophils to bind PAF was rapidly diminished upon cell stimulation with both physiological agonists (N-formylmethionylleucylphenylalanine (FMLP), leukotriene B4(LTB4)) and pharmacologic agonists (phorbol 12-myristate 13-acetate (PMA), A23187). As a consequence, PAF responses in neutrophils were blunted, as monitored by an inhibition of intracellular Ca2+mobilization. Downregulation of the PAF receptor in neutrophils by diverse agonists was temperature-sensitive and required intact cells. Scatchard analysis of binding data revealed that PAF binding sites were lost without an appreciable change in the affinity of the ligand for the receptor. The binding of the PAF receptor antagonist WEB2086 to neutrophils decreased in parallel with PAF binding. PMA-induced PAF receptor downregulation was stauro-sporine-sensitive while PAF receptor downregulation by A23187, FMLP, or LTB4was staurosporine-resistant. Both neutrophil aggregation (a form of intercellular adhesion) and PAF receptor downregulation occurred only at high concentrations of agonists while other signaling processes such as the increase in [Ca2+]i, PKC activation, and PAF synthesis were stimulated at low concentrations of agonists. Furthermore, agonist-induced PAF receptor downregulation was observed only under conditions in which the activated neutrophils were stirred (or shaken) and were allowed to aggregate. Additionally, chelation of extracellular Ca2+with EGTA minimized cell aggregation and also inhibited PAF receptor downregulation. While the nature of the biochemical signal or the physical changes in the plasma membrane associated with aggregation or that follow aggregation remain to be elucidated, it is clear that full expression of cell activation (i.e., neutrophil aggregation) is required for PAF receptor downregulation.