MECHANISM OF NEUTROPHIL ACTIVATION BY NAF, A NOVEL MONOCYTE-DERIVED PEPTIDE AGONIST
MECHANISM OF NEUTROPHIL ACTIVATION BY NAF, A NOVEL MONOCYTE-DERIVED PEPTIDE AGONIST
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DOI：
10.1096/fasebj.2.11.2840318
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发表时间：
1988-08-01
期刊：
影响因子：
4.8
通讯作者：
BAGGIOLINI, M
中科院分区：
文献类型：
--
作者：
THELEN, M;PEVERI, P;BAGGIOLINI, M
比较了N-甲酰-蛋氨酸-亮氨酸-苯丙氨酸(FMLP)和新发现的中性粒细胞激活因子NaF对中性粒细胞内游离钙离子浓度升高、形态改变、超氧化物形成和颗粒生成的影响。NaF在0.1-10 nM的浓度范围内有效，是fMLP的10-100倍。在定性方面，对两种刺激的单一反应非常相似：它们表现出几乎相同的起效和初始动力学，并且都被百日咳杆菌毒素预处理的中性粒细胞所抑制。此外，两种刺激引起的呼吸爆发均可被17-羟基Wortmannin和星形孢子素抑制。这些结果得出两个结论：1)NaF(如fMLP)对中性粒细胞的激活依赖于GTP结合蛋白和蛋白激酶C；2)用NaF、fMLP和其他趋化激动剂刺激中性粒细胞，必须假设类似甚至相同的信号转导机制。人单核细胞、淋巴细胞和血小板在氟化钠作用下未见胞浆游离钙离子的变化，说明氟化钠对中性粒细胞具有选择性。
The rise in cytosolic free Ca2+, shape change, superoxide formation, and granule eoxytosis induced in human neutrophils by N-formyl-Met-Leu-Phe (fMLP) and by a newly discovered activating peptide, neutrophil-activating factor, termed NAF, were compared. NAF was effective in the concentration range of 0.1-10 nM and was 10- to 100-fold more potent than fMLP. In qualitative terms, the single responses to either stimulus were remarkably similar: they showed virtually identical onset and initial kinetics, and were all inhibited by pretreatment of the neutrophils with Bordetella pertussis toxin. In addition, the respiratory burst elicited by either stimulus was inhibited by 17-hydroxywortmannin and staurosporine. Two conclusions are drawn from these results: 1) neutrophil activation by NAF (as by fMLP) is dependent on a GTP-binding protein and on protein kinase C; 2) a similar, or even identical, mechanism of signal transduction must be assumed on stimulation of human neutrophils with NAF, fMLP, and other chemotactic agonists. Human monocytes, lymphocytes, and platelets did not show cytosolic free Ca2+ changes when exposed to NAF, which suggests that NAF is selective for the neutrophils.