Identification of novel chemoattractant peptides for human leukocytes
Identification of novel chemoattractant peptides for human leukocytes
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DOI：
10.1182/blood.v97.9.2854
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发表时间：
2001-05-01
期刊：
影响因子：
20.3
通讯作者：
Ryu, SH
中科院分区：
文献类型：
--
作者：
Bae, YS;Bae, H;Ryu, SH
超氧化物是单核细胞抵御病原体侵袭的主要防线上最重要的军械库，识别新的刺激和表征超氧化物产生的调节机制至关重要。在这项研究中，我们通过筛选一个合成的六肽组合文库和对其中1个肽的修饰，鉴定了3个新的肽。分离到的能诱导人单核细胞产生超氧化物的肽有his - ph - tyr - leu - pro - met - conh2 （HFYLPM）、met - ph - tyr - leu - pro - d - conh2 （MFYLPM）和his - ph - tyr - leu - pro - d - met - conh2 （HFYLPM）。3种多肽均引起细胞内钙（[ca++](i)）升高。我们通过观察[Ca++](i)上升来测试肽在不同来源细胞上的特异性。这3种肽均对白细胞有特异性作用，对非免疫细胞无特异性作用。在白细胞中，MFYLPM和HFYLPM分别对HL60和Jurkat T细胞有特异性刺激。作为肽的生理特性，我们观察到这3种肽都能诱导单核细胞的趋化迁移，研究受体特异性，我们得出结论，这3种肽可能作用于白细胞上的一些共同的和不同的受体。通过研究这些多肽在细胞内的信号传导机制，我们发现HFYLPM，而不是MFYLPM或HFYLPM，通过磷酸肌醇-3激酶和蛋白激酶c诱导趋化。因为HFYLPM、MFYLPM和HFYLPM不仅根据细胞类型和分化状态表现出不同的特异性，而且还通过不同的受体和信号传导刺激细胞，这3种多肽可能是研究白细胞活化的有用工具。（Blood. 2001; 97:2854-2862） (C) 2001年由美国血液学会出版。
Superoxide is the most important armory on the primary defense line of monocytes against invading pathogens, and the identification of new stimuli and the characterization of the regulatory mechanism of superoxide generation are of paramount importance. In this study, we identified 3 novel peptides by screening a synthetic hexapeptide combinatorial library and modification of 1 of the peptides. The isolated peptides that can induce superoxide generation in human monocytes are His-Phe-Tyr-Leu-Pro-Met-CONH2 (HFYLPM), Met-Phe-Tyr-Leu-Pro-D-CONH2 (MFYLPM), and His-Phe-Tyr-Leu-Pro-D-Met-CONH2 (HFYLPm). All 3 peptides also caused intracellular calcium ([Ca++](i)) rise. We tested the specificities of the peptides on cells of different origin by looking at [Ca++](i) rise. All 3 peptides acted specifically on leukocytes and not on nonimmune cells, Among leukocytes, HL60 and Jurkat T cells were stimulated specifically by MFYLPM or HFYLPM, respectively. As a physiologic characteristic of the peptides, we observed that all 3 peptides induced chemotactic migration of monocytes, Studying receptor specificity, we concluded that the 3 peptides might act on some shared and some distinct receptor(s) on leukocytes. Studying intracellular signaling set in motion by the peptides revealed that HFYLPM, but not MFYLPM or HFYLPm, induced chemotaxis via phospatidylinositol-3 kinase and protein kinase C. Because HFYLPM, MFYLPM, and HFYLPm not only exhibit different specificities depending on cell type and status of differentiation but also stimulate cells via distinct receptors and signaling, the 3 never peptides might be useful tools to study leukocyte activation. (Blood. 2001; 97:2854-2862) (C) 2001 by The American Society of Hematology.