Phospholipid metabolism in human neutrophils activated by N-formyl-methionyl-leucyl-phenylalanine. Degranulation is not required for release of arachidonic acid: studies with neutrophils and neutrophil-derived cytoplasts.
Phospholipid metabolism in human neutrophils activated by N-formyl-methionyl-leucyl-phenylalanine. Degranulation is not required for release of arachidonic acid: studies with neutrophils and neutrophil-derived cytoplasts.
复制标题
N-甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸激活人中性粒细胞中的磷脂代谢。
DOI：
10.1042/bj2360829
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Weissmann,G
中科院分区：
文献类型：
--
作者：
Wynkoop,EM;Broekman,MJ;Korchak,HM;Marcus,AJ;Weissmann,G
中性粒细胞通过聚集、脱粒、重塑磷脂和释放花生四烯酸对化学引诱物作出反应。为了确定配体诱导的磷脂重塑是否依赖于细胞内细胞器的再分布（脱粒），我们比较了人中性粒细胞的磷脂重塑与嗜中性粒细胞衍生的胞质体。细胞质是被质膜包围的细胞质溶胶中的细胞器耗尽的小泡，不能脱泡。没有刺激，[3 H]花生四烯酸优先纳入磷脂酰肌醇（PI）和磷脂酰胆碱（PC）。将预先用[3 H]花生四烯酸或[14 C]甘油标记的细胞质和中性粒细胞暴露于fMet-Leu-Phe（10（-7）M），诱导标记物分布和单个磷脂质量的快速变化：[~ 3 H]花生四烯酸在磷脂酸（PA）中的含量增加了500%（120 s），[~（14）C]甘油掺入和PA质量接近未刺激值的200%，和[3 H]花生四烯酸在PI持续下降，这些数据与PI/PA循环的活动相一致。然而，PI的质量在两个制剂和[14 C]甘油标记在完整的中性粒细胞增加最初（5秒），表明净合成和动员一个以上的池的PI。还观察到PC池的异源性：[3 H]花生四烯酸在加入刺激后立即从PC中丢失，而质量和[14 C]甘油值增加。因此，净磷脂合成，花生四烯酸盐的再分配和PI/PA循环的激活是中性粒细胞对化学引诱物的受体占据的立即反应。此外，中性粒细胞和无颗粒细胞质对fMet-Leu-Phe反应的相似性表明这些过程不依赖于脱粒。
Neutrophils respond to chemoattractants by aggregating, degranulating, remodelling of phospholipids and releasing arachidonic acid. To determine whether ligand-induced remodelling of phospholipids depends on redistribution of intracellular organelles (degranulation), we compared phospholipid remodelling of human neutrophils with that of neutrophil-derived cytoplasts. Cytoplasts, organelle-depleted vesicles of cytosol surrounded by plasmalemma, cannot degranulate. Without a stimulus, [3H]arachidonate was incorporated preferentially into phosphatidylinositol (PI) and phosphatidylcholine (PC). Exposure of cytoplasts and neutrophils prelabelled with [3H]arachidonate or [14C]glycerol to fMet-Leu-Phe (10(-7) M) induced rapid changes in distribution of label and mass of individual phospholipids: [3H]arachidonate in phosphatidic acid (PA) increased 500% (120 s), [14C]glycerol incorporation and mass of PA approached 200% of unstimulated values, and [3H]arachidonate in PI decreased continuously; these data are compatible with activity of a PI/PA cycle. However, the mass of PI in both preparations and [14C]glycerol label in intact neutrophils increased initially (5 s), suggesting net synthesis and mobilization of more than one pool of PI. Heterogeneity of PC pools was also observed: [3H]arachidonate was lost from PC immediately upon addition of stimulus, whereas mass and [14C]glycerol values increased. Thus, net phospholipid synthesis, redistribution of arachidonate and activation of the PI/PA cycle are immediate responses of the neutrophil to receptor occupancy by chemoattractants. Furthermore, the similarity in response to fMet-Leu-Phe of neutrophils and granule-free cytoplasts indicates that these processes are independent of degranulation.