Teresi S, Boudard F, Bastide M
Immunology and Parasitology Laboratory, University of Montpellier I, Faculty of Pharmacy, France.
Immunol Lett. 1996 Apr;50(1-2):105-13. doi: 10.1016/0165-2478(96)02524-2.
The effects of alpha calcitonin gene-related peptide (alpha CGRP) and vasoactive intestinal peptide (VIP) on the proliferation of CD4 and CD8 T-murine lymphocytes were investigated. When stimulated by a combination of phorbol 12-myristate-13-acetate (PMA) and calcium ionophore (A23187), both neuropeptides in a range of 10(-7)-10(-10) M had an inhibitory effect on the proliferative response of unfractionated splenocytes as well as of purified CD4 and CD8 T lymphocytes. The inhibitory effect of these two neuropeptides was completely or partially blocked by the antagonists of CGRP and VIP receptors. CGRP8-37 and (p-Cl-D-Phe6, Leu17VIP, respectively. The inhibitory effects of each neuropeptide on purified T cells were observed within 4 h after PMA/A23187 activation and their inhibitory actions were correlated with a decrease of IL-2 production. In addition, the two neuropeptides in a range of 10(-7)-10(-10) M induced a rapid and dose-dependent increase in intracellular cAMP in CD4 and CD8 T cells. This suggests the involvement of this second messenger in the inhibitory effects of these two neuropeptides. Taken together these results show that CD4 and CD8 spleen cells represent at least two of the cellular targets for CGRP and VIP inhibition of proliferation mediated by the same type of mechanism.
研究了α降钙素基因相关肽（αCGRP）和血管活性肠肽（VIP）对小鼠CD4和CD8 T淋巴细胞增殖的影响。当用佛波醇12 - 肉豆蔻酸酯 - 13 - 乙酸酯（PMA）和钙离子载体（A23187）联合刺激时，浓度范围为10^(-7) - 10^(-10) M的这两种神经肽对未分离的脾细胞以及纯化的CD4和CD8 T淋巴细胞的增殖反应均有抑制作用。这两种神经肽的抑制作用被CGRP和VIP受体拮抗剂完全或部分阻断，分别为CGRP8 - 37和（对氯 - D - 苯丙氨酸6，亮氨酸17）VIP。每种神经肽对纯化T细胞的抑制作用在PMA/A23187激活后4小时内即可观察到，其抑制作用与IL - 2产生的减少相关。此外，浓度范围为10^(-7) - 10^(-10) M的这两种神经肽可诱导CD4和CD8 T细胞内cAMP迅速且呈剂量依赖性增加。这表明这种第二信使参与了这两种神经肽的抑制作用。综合这些结果表明，CD4和CD8脾细胞是CGRP和VIP通过同一机制抑制增殖作用的至少两个细胞靶点。
