Soares M B, Titus R G, Shoemaker C B, David J R, Bozza M
Department of Tropical Public Health, Harvard School of Public Health, Boston, MA 02115, USA.
J Immunol. 1998 Feb 15;160(4):1811-6.
Maxadilan is a vasodilatory peptide encoded by a gene cloned from Lutzomyia longipalpis salivary glands. In this study we investigated the effects of maxadilan on macrophage functions. Maxadilan treatment of LPS-stimulated BALB/c macrophages inhibited TNF-alpha release but increased IL-6. Further, it also induced IL-6 release in a dose-dependent manner from unstimulated macrophages. Maxadilan increased production of PGE2, and the inhibition of TNF-alpha was completely abrogated by indomethacin. Others have recently shown that maxadilan is a selective agonist of the pituitary adenylate cyclase-activating polypeptide (PACAP) type I receptor. Treatment with the receptor antagonist PACAP 6-38 blocked maxadilan activities on macrophages. The natural endogenous ligand, PACAP 38, had the same effects as maxadilan on TNF-alpha and IL-6 production. Finally, in a dose- and time-dependent fashion, maxadilan induced the intracellular accumulation of cAMP in macrophages. Taken together, the results presented here indicate a modulatory effect of ligands of PACAP type I receptor on cytokine production by macrophages and suggest that activation of this receptor, with the subsequent elevation of intracellular cAMP in macrophages, could participate in a negative-feedback mechanism that controls certain inflammatory responses.
麦克斯迪兰是一种血管舒张肽，由从长须罗蛉唾液腺克隆的基因编码。在本研究中，我们研究了麦克斯迪兰对巨噬细胞功能的影响。用麦克斯迪兰处理脂多糖刺激的BALB/c巨噬细胞可抑制肿瘤坏死因子-α（TNF-α）的释放，但会增加白细胞介素-6（IL-6）的释放。此外，它还能以剂量依赖的方式诱导未受刺激的巨噬细胞释放IL-6。麦克斯迪兰增加了前列腺素E2（PGE2）的产生，吲哚美辛可完全消除其对TNF-α的抑制作用。最近其他人表明，麦克斯迪兰是垂体腺苷酸环化酶激活多肽（PACAP）I型受体的选择性激动剂。用受体拮抗剂PACAP 6-38处理可阻断麦克斯迪兰对巨噬细胞的作用。天然内源性配体PACAP 38对TNF-α和IL-6的产生具有与麦克斯迪兰相同的作用。最后，麦克斯迪兰以剂量和时间依赖的方式诱导巨噬细胞内cAMP的积累。综上所述，此处呈现的结果表明PACAP I型受体配体对巨噬细胞产生细胞因子具有调节作用，并表明该受体的激活以及随后巨噬细胞内cAMP的升高可能参与控制某些炎症反应的负反馈机制。
