Tou Jen Sie
Department of Biochemistry, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, Louisiana 70112, USA.
Biochem Biophys Res Commun. 2002 Apr 12;292(4):951-6. doi: 10.1006/bbrc.2002.6765.
One of the proposed functions of phosphatidic acid (PA) formation from phospholipase D (PLD) activation in neutrophils is to promote degranulation induced by receptor agonists. The present study shows that the time course and dose response of PA formation and degranulation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) differed. PLD activation and degranulation also exhibited different dose response to genistein and epigallocatechin gallate (EGCG), inhibitors of protein tyrosine kinases. Genistein inhibited PLD activity with an IC(50) value of 12.2 microM in fMLP- and 107 microM in phorbol myristate acetate (PMA)-stimulated cells. It required higher concentrations of genistein to inhibit degranulation than to inhibit PLD activity induced by fMLP. EGCG in the range of 40-400 microM had no effect on PLD activity but it inhibited the release of beta-glucuronidase and elastase by fMLP-stimulated cells. These results demonstrate differential regulation of PLD activity and degranulation of primary granules by genistein and EGCG in fMLP-stimulated neutrophils.
中性粒细胞中磷脂酶D（PLD）激活形成磷脂酸（PA）的一个推测功能是促进受体激动剂诱导的脱颗粒作用。本研究表明，N-甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）诱导的PA形成和脱颗粒的时间进程和剂量反应有所不同。PLD激活和脱颗粒对蛋白酪氨酸激酶抑制剂染料木黄酮和表没食子儿茶素没食子酸酯（EGCG）也表现出不同的剂量反应。在fMLP刺激的细胞中，染料木黄酮抑制PLD活性的IC（50）值为12.2微摩尔，在佛波酯（PMA）刺激的细胞中为107微摩尔。抑制脱颗粒所需的染料木黄酮浓度高于抑制fMLP诱导的PLD活性所需的浓度。40 - 400微摩尔范围内的EGCG对PLD活性无影响，但它抑制fMLP刺激的细胞释放β-葡萄糖醛酸酶和弹性蛋白酶。这些结果表明，在fMLP刺激的中性粒细胞中，染料木黄酮和EGCG对PLD活性和初级颗粒脱颗粒有不同的调节作用。
