Iwamoto I, Yamazaki H, Nakagawa N, Kimura A, Tomioka H, Yoshida S
Second Department of Internal Medicine, Chiba University School of Medicine, Japan.
Neuropeptides. 1990 Jun;16(2):103-7. doi: 10.1016/0143-4179(90)90119-j.
To determine the mechanism by which substance P (SP) activates human neutrophils, we examined the potencies of SP, the C-terminal peptides SP4-11 and SP6-11, and the N-terminal peptides SP1-9 and SP1-4 for inducing the increase in cytosolic free Ca2+ concentration ([Ca2+]i), superoxide (O2-) generation, and chemotaxis in human blood neutrophils. SP and the C-terminal peptides SP4-11 and SP6-11 and SP6-11 (10(-6)-10(-4) M) induced the increase in ([Ca2+]i, O2- generation, and chemotaxis of the neutrophils dose--dependently, whereas the N-terminal peptides SP1-9 and SP1-4 (up to 10(-4) M) were inactive in inducing these responses. Furthermore, the potencies of the two C-terminal peptides SP4-11 and SP6-11 were not parallel in these three responses. SP6-11 was 7.7-fold more potent in increasing [Ca2+]i than SP4-11, whereas SP4-11 was 16.6-fold more potent in inducing O2-generation than SP6-11. SP6-11 was also 2.1-fold more potent in inducing chemotaxis than SP4-11. Thus, we conclude that the C-terminal peptides of SP induce differential activations of human neutrophils.
为了确定P物质(SP)激活人中性粒细胞的机制,我们检测了SP、C末端肽SP4 - 11和SP6 - 11以及N末端肽SP1 - 9和SP1 - 4在人血中性粒细胞中诱导胞质游离钙浓度([Ca2+]i)升高、超氧化物(O2-)生成和趋化性的效能。SP以及C末端肽SP4 - 11、SP6 - 11(10(-6)-10(-4) M)可剂量依赖性地诱导中性粒细胞的[Ca2+]i升高、O2-生成和趋化性,而N末端肽SP1 - 9和SP1 - 4(高达10(-4) M)在诱导这些反应方面无活性。此外,两种C末端肽SP4 - 11和SP6 - 11在这三种反应中的效能并不平行。SP6 - 11在增加[Ca2+]i方面的效能比SP4 - 11高7.7倍,而SP4 - 11在诱导O2-生成方面的效能比SP6 - 11高16.6倍。SP6 - 11在诱导趋化性方面的效能也比SP4 - 11高2.1倍。因此,我们得出结论,SP的C末端肽可诱导人中性粒细胞的不同激活。