Regulation of phospholipase D and primary granule secretion by P2-purinergic- and chemotactic peptide-receptor agonists is induced during granulocytic differentiation of HL-60 cells.
Regulation of phospholipase D and primary granule secretion by P2-purinergic- and chemotactic peptide-receptor agonists is induced during granulocytic differentiation of HL-60 cells.
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P2 嘌呤能受体激动剂和趋化肽受体激动剂对磷脂酶 D 和初级颗粒分泌的调节是在 HL-60 细胞的粒细胞分化过程中诱导的。
DOI：
10.1172/jci115303
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Dubyak,GR
中科院分区：
文献类型：
--
作者：
Xie,MS;Jacobs,LS;Dubyak,GR
我们比较了细胞外ATP（通过p2 -嘌呤能受体作用）和甲酰化肽（FMLP）刺激HL-60细胞沿粒细胞途径诱导分化的磷脂酶D （PLD）信号转导和原代颗粒（亲氮）分泌的能力。在未分化的HL-60细胞中，ATP和FMLP都没有引起显著的PLD激活或分泌增加，尽管之前有文献证明ATP能够刺激多磷酸肌醇水解和Ca2+动员的大量增加。相反，在二丁基cAMP诱导粒细胞分化后的1 d内，ATP和FMLP均诱导azuroophilic分泌大量增加，PLD活性相应增加。二丁基cAMP处理后1 d内，ATP激活的PLD活性接近峰值，而fmlp诱导的PLD活性在4 d内持续增加，峰值水平是ATP刺激的2倍。其他实验表征了PLD在不同分化阶段通过受体独立途径激活；这些研究包括完整细胞中的佛波酯作用和电渗透细胞中的GTP γ S作用。在百日咳毒素预处理的细胞中，观察到FMLP和atp刺激的PLD活性显著降低，也表明鸟嘌呤核苷酸结合调节蛋白在PLD调节中的明显作用。在分化的所有阶段，ATP与FMLP在刺激分泌和PLD活性方面的相对功效之间存在良好的相关性。这些数据表明：(a)受体调控的磷脂酶D信号通路在髓系祖细胞分化过程中被诱导；(b)各种Ca（2+）动员受体激动剂对该信号系统的不同激活可能是这些药物对分泌和其他吞噬细胞功能的差异调节的基础。
We have compared the abilities of extracellular ATP (acting via P2-purinergic receptors) and formylated peptides (FMLP) to stimulate both phospholipase D (PLD)-based signal transduction and primary granule (azurophilic) secretion in HL-60 cells induced to differentiate along the granulocytic pathway. In undifferentiated HL-60 cells, neither ATP nor FMLP elicited significant PLD activation or increased secretion despite the previously documented ability of ATP to stimulate large increases in polyphosphoinositide hydrolysis and Ca2+ mobilization. Conversely, within 1 d after induction of granulocytic differentiation by dibutyryl cAMP, both ATP and FMLP induced large increases in azurophilic secretion and corresponding increases in PLD activity. ATP-activated PLD activity was near-maximal within 1 d after dibutyryl cAMP treatment, while the FMLP-induced activity increased continuously over 4 d, with a maximal level twice that stimulated by ATP. Additional experiments characterized the activation of PLD by receptor-independent pathways at different stages of differentiation; these included studies of phorbol ester action in intact cells and GTP gamma S action in electropermeabilized cells. An apparent role for guanine nucleotide-binding regulatory proteins in PLD regulation was also indicated by the significant reduction in FMLP- and ATP-stimulated PLD activity observed in cells pretreated with pertussis toxin. At all stages of differentiation, there was good correlation between the relative efficacies of ATP versus FMLP in stimulating both secretion and PLD activity. These data indicate: (a) that the receptor-regulated phospholipase D signaling pathway is induced during differentiation of myeloid progenitor cells; and (b) that differential activation of this signaling system by various Ca(2+)-mobilizing receptor agonists may underlie the differential regulation of secretion and other phagocyte functions by such agents.