沙蚕毒素抑制人外周血淋巴细胞的增殖及白细胞介素2的产生。
Charybdotoxin inhibits proliferation and interleukin 2 production in human peripheral blood lymphocytes.
作者信息
Price M, Lee S C, Deutsch C
机构信息
Department of Physiology, University of Pennsylvania, Philadelphia 19104-6085.
出版信息
Proc Natl Acad Sci U S A. 1989 Dec;86(24):10171-5. doi: 10.1073/pnas.86.24.10171.
Abstract
We demonstrate that blockade of the lymphocyte voltage-gated K+ channel by charybdotoxin (CTX) inhibits lymphocyte mitogenesis. Charybdotoxin blocks conductance with a Ki of 0.3 nM and inhibits mitogen- and antigen-stimulated proliferation with a Ki of 0.5 nM. As opposed to the other blockers of the lymphocyte K+ channel, the inhibition of mitogenesis by CTX can be overcome selectively by exogenous recombinant interleukin 2 (IL-2); endogenous levels of IL-2 in the culture supernatants of stimulated cells are decreased by the presence of CTX. Our results suggest that the voltage-gated K+ channel is either directly or indirectly involved in IL-2 synthesis and/or secretion.
摘要
我们证明，用蝎毒素（CTX）阻断淋巴细胞电压门控钾通道可抑制淋巴细胞有丝分裂。蝎毒素以0.3 nM的抑制常数（Ki）阻断离子传导，并以0.5 nM的Ki抑制有丝分裂原和抗原刺激的增殖。与淋巴细胞钾通道的其他阻断剂不同，外源性重组白细胞介素2（IL-2）可选择性地克服CTX对有丝分裂的抑制作用；刺激细胞培养上清液中IL-2的内源性水平因CTX的存在而降低。我们的结果表明，电压门控钾通道直接或间接参与IL-2的合成和/或分泌。
相似文献
1
Charybdotoxin inhibits proliferation and interleukin 2 production in human peripheral blood lymphocytes.沙蚕毒素抑制人外周血淋巴细胞的增殖及白细胞介素2的产生。
Proc Natl Acad Sci U S A. 1989 Dec;86(24):10171-5. doi: 10.1073/pnas.86.24.10171.
2
Blocking of human T lymphocyte activation by channel antagonists.通道拮抗剂对人T淋巴细胞活化的阻断作用。
Cell Biochem Funct. 1989 Jul;7(3):219-26. doi: 10.1002/cbf.290070311.
3
4
Calcium-mediated agonists activate an inwardly rectified K+ channel in colonic secretory cells.钙介导的激动剂激活结肠分泌细胞中的内向整流钾通道。
Am J Physiol. 1993 Nov;265(5 Pt 1):C1271-80. doi: 10.1152/ajpcell.1993.265.5.C1271.
5
Selective blockers of voltage-gated K+ channels depolarize human T lymphocytes: mechanism of the antiproliferative effect of charybdotoxin.电压门控钾通道的选择性阻滞剂使人类T淋巴细胞去极化：大蝎毒素抗增殖作用的机制
Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10094-8. doi: 10.1073/pnas.89.21.10094.
6
Evidence for voltage modulation of IL-2 production in mitogen-stimulated human peripheral blood lymphocytes.丝裂原刺激的人外周血淋巴细胞中白细胞介素-2产生的电压调节证据。
J Immunol. 1992 Dec 15;149(12):3784-94.
7
Autologous mixed-lymphocyte reaction in man. XVII. In vitro effect of ion channel-blocking agents on the autologous mixed-lymphocyte response.人类自体混合淋巴细胞反应。第十七部分。离子通道阻滞剂对自体混合淋巴细胞反应的体外效应。
Cell Immunol. 1987 Feb;104(2):290-5. doi: 10.1016/0008-8749(87)90031-1.
8
Stage-specific distinctions in potassium channel blocker control of T-lymphocyte activation.钾通道阻滞剂对T淋巴细胞激活的阶段特异性调控差异
Int J Immunopharmacol. 1988;10(3):217-26. doi: 10.1016/0192-0561(88)90052-5.
9
10
Voltage-gated potassium channels regulate calcium-dependent pathways involved in human T lymphocyte activation.电压门控钾通道调节参与人类T淋巴细胞激活的钙依赖性途径。
J Exp Med. 1993 Mar 1;177(3):637-45. doi: 10.1084/jem.177.3.637.
引用本文的文献
1
Disease-associated Kv1.3 Variants are Energy Compromised with Impaired Nascent Chain Folding.与疾病相关的Kv1.3变体能量受损，新生链折叠也受到损害。
J Mol Biol. 2025 Sep 1;437(17):169226. doi: 10.1016/j.jmb.2025.169226. Epub 2025 May 21.
2
Immunomodulatory effect of sp. in mononuclear cells extracted from the blood of rheumatoid arthritis patients.[某种物种]对类风湿关节炎患者血液中提取的单核细胞的免疫调节作用
J Venom Anim Toxins Incl Trop Dis. 2024 Sep 16;30:e20230064. doi: 10.1590/1678-9199-JVATITD-2023-0064. eCollection 2024.
3
Structure of the voltage-gated potassium channel K1.3: Insights into the inactivated conformation and binding to therapeutic leads.电压门控钾通道 K1.3 的结构：失活构象的深入了解及与治疗先导物的结合。
Channels (Austin). 2023 Dec;17(1):2253104. doi: 10.1080/19336950.2023.2253104.
4
The Interaction between hERG1 and β1 Integrins Modulates hERG1 Current in Different Pathological Cell Models.hERG1与β1整合素之间的相互作用在不同病理细胞模型中调节hERG1电流。
Membranes (Basel). 2022 Nov 18;12(11):1162. doi: 10.3390/membranes12111162.
5
Structures of the T cell potassium channel Kv1.3 with immunoglobulin modulators.T 细胞钾通道 Kv1.3 与免疫球蛋白调节剂的结构。
Nat Commun. 2022 Jul 4;13(1):3854. doi: 10.1038/s41467-022-31285-5.
6
Anti-Inflammatory Effect of Licochalcone A via Regulation of ORAI1 and K Channels in T-Lymphocytes.甘草查尔酮 A 通过调节 T 淋巴细胞中的 ORAI1 和 K 通道发挥抗炎作用。
Int J Mol Sci. 2021 Oct 7;22(19):10847. doi: 10.3390/ijms221910847.
7
Cytometrical analysis of the adverse effects of indican, indoxyl, indigo, and indirubin on rat thymic lymphocytes.靛基质、吲哚酚、靛蓝和靛玉红对大鼠胸腺淋巴细胞不良反应的细胞计量分析
Toxicol Res (Camb). 2018 Mar 28;7(3):513-520. doi: 10.1039/c7tx00244k. eCollection 2018 May 8.
8
7DHC-induced changes of Kv1.3 operation contributes to modified T cell function in Smith-Lemli-Opitz syndrome.7-脱氢胆固醇（7DHC）诱导的Kv1.3通道功能变化导致了史密斯-勒米-奥皮茨综合征中T细胞功能的改变。
Pflugers Arch. 2016 Aug;468(8):1403-18. doi: 10.1007/s00424-016-1851-4. Epub 2016 Jun 17.
9
Lovastatin blocks Kv1.3 channel in human T cells: a new mechanism to explain its immunomodulatory properties.洛伐他汀阻断人T细胞中的Kv1.3通道：一种解释其免疫调节特性的新机制。
Sci Rep. 2015 Nov 30;5:17381. doi: 10.1038/srep17381.
10
Usefulness of targeting lymphocyte Kv1.3-channels in the treatment of respiratory diseases.靶向淋巴细胞Kv1.3通道在呼吸系统疾病治疗中的应用价值。
Inflamm Res. 2015 Oct;64(10):753-65. doi: 10.1007/s00011-015-0855-4. Epub 2015 Jul 24.
本文引用的文献
1
Role of membrane potential in the regulation of lectin-induced calcium uptake.膜电位在凝集素诱导的钙摄取调节中的作用。
J Cell Physiol. 1984 Dec;121(3):533-9. doi: 10.1002/jcp.1041210312.
2
Interleukin 2.白细胞介素2
Annu Rev Immunol. 1984;2:319-33. doi: 10.1146/annurev.iy.02.040184.001535.
3
K channels in T lymphocytes: a patch clamp study using monoclonal antibody adhesion.T淋巴细胞中的钾通道：一项使用单克隆抗体黏附的膜片钳研究。
Nature. 1984;307(5950):468-71. doi: 10.1038/307468a0.
4
Lymphocyte membrane potential assessed with fluorescent probes.用荧光探针评估淋巴细胞膜电位。
Biochim Biophys Acta. 1980;595(1):15-30. doi: 10.1016/0005-2736(80)90243-6.
5
Voltage-gated potassium channels are required for human T lymphocyte activation.电压门控钾通道是人类T淋巴细胞激活所必需的。
J Exp Med. 1984 Aug 1;160(2):369-85. doi: 10.1084/jem.160.2.369.
6
7
8
Voltage-gated potassium conductance in human T lymphocytes stimulated with phorbol ester.佛波酯刺激的人T淋巴细胞中的电压门控钾电导
J Physiol. 1986 Mar;372:405-23. doi: 10.1113/jphysiol.1986.sp016016.
9
Volume response of quiescent and interleukin 2-stimulated T-lymphocytes to hypotonicity.
Am J Physiol. 1988 Feb;254(2 Pt 1):C286-96. doi: 10.1152/ajpcell.1988.254.2.C286.
10
Requirement for extracellular calcium or magnesium in mitogen-induced activation of human peripheral blood lymphocytes.丝裂原诱导的人外周血淋巴细胞活化过程中对细胞外钙或镁的需求。
J Cell Physiol. 1988 Jun;135(3):451-8. doi: 10.1002/jcp.1041350312.
Zotero 插件