非典型蛋白激酶C（PKC ζ）在调节人类嗜酸性粒细胞和中性粒细胞功能中的差异作用。
Differential role of an atypical protein kinase C, PKC zeta, in regulation of human eosinophil and neutrophil functions.
作者信息
Kato Masahiko, Yamaguchi Takafumi, Tachibana Atsushi, Kimura Hirokazu
机构信息
Department of Allergy and Immunology, Gunma Children's Medical Center, Hokkitsu, Japan.
出版信息
Int Arch Allergy Immunol. 2005;137 Suppl 1:27-34. doi: 10.1159/000085429. Epub 2005 Jun 2.
BACKGROUND
Protein kinase C (PKC) comprises a family of isoenzymes playing a key role in downstream signaling and cell functions. PKCs are grouped according to molecular structure and mode of activation: 'conventional' PKCs (alpha, betaI, betaII, gamma), 'novel' PKCs (delta, epsilon, mu, theta, eta), and 'atypical' PKCs (zeta, tau/lambda). Here we compared the influence of PKC zeta on the function of human eosinophils and neutrophils.
METHODS
After pretreating the cells with a myristoylated specific PKC zeta inhibitor, a myristoylated PKC eta inhibitor, or bisindolylmaleimide I (Bis I; an inhibitor of conventional and novel PKCs), we examined N-formyl-methionyl-leucyl-phenylalanine (FMLP)- or 4-phorbol 12-myristate 13-acetate (PMA)-evoked superoxide anion (O(2)(-)) generation. Induced PKC translocation was characterized using confocal laser scanning microscopy.
RESULTS
The PKC zeta inhibitor significantly blocked FMLP- or PMA-induced O(2)(-) generation by eosinophils. However, this inhibitor attenuated PMA- but not FMLP-induced O(2)(-) generation by neutrophils. In contrast, Bis I inhibited FMLP-induced O(2)(-) generation by eosinophils and neutrophils in a similar manner. The PKC eta inhibitor had no significant effect, since both cell types lack PKC eta; this confirmed specificity of PKC zeta inhibitor effects. Finally, the translocation of PKC zeta to the plasma membrane induced by FMLP in both eosinophils and neutrophils was started at 1 min while the translocation was maintained for 15 min in eosinophils but not in neutrophils.
CONCLUSION
An atypical PKC, PKC zeta, regulates human eosinophil and neutrophil functions in a differential manner.
背景
蛋白激酶C（PKC）是一组同工酶，在下游信号传导和细胞功能中起关键作用。PKC根据分子结构和激活方式进行分类：“传统”PKC（α、βI、βII、γ）、“新型”PKC（δ、ε、μ、θ、η）和“非典型”PKC（ζ、τ/λ）。在此，我们比较了PKCζ对人嗜酸性粒细胞和中性粒细胞功能的影响。
方法
用肉豆蔻酰化的特异性PKCζ抑制剂、肉豆蔻酰化的PKCη抑制剂或双吲哚马来酰亚胺I（Bis I；传统和新型PKC的抑制剂）预处理细胞后，我们检测了N-甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）或4-佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）诱导的超氧阴离子（O₂⁻）生成。使用共聚焦激光扫描显微镜对诱导的PKC易位进行表征。
结果
PKCζ抑制剂显著阻断了嗜酸性粒细胞由FMLP或PMA诱导的O₂⁻生成。然而，该抑制剂减弱了中性粒细胞由PMA而非FMLP诱导的O₂⁻生成。相比之下，Bis I以类似方式抑制嗜酸性粒细胞和中性粒细胞由FMLP诱导的O₂⁻生成。PKCη抑制剂没有显著作用，因为两种细胞类型都缺乏PKCη；这证实了PKCζ抑制剂作用的特异性。最后，FMLP在嗜酸性粒细胞和中性粒细胞中诱导的PKCζ向质膜的易位在1分钟时开始，而在嗜酸性粒细胞中易位持续15分钟，在中性粒细胞中则不然。
结论
一种非典型PKC，即PKCζ，以不同方式调节人嗜酸性粒细胞和中性粒细胞的功能。
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