Regulation of endothelial production of C-type natriuretic peptide by interaction between endothelial cells and macrophages.
Regulation of endothelial production of C-type natriuretic peptide by interaction between endothelial cells and macrophages.
复制标题
DOI：
10.1210/endo.139.4.5918
复制
发表时间：
1998-04
期刊：
影响因子：
4.8
通讯作者：
S. Suga;H. Itoh;Y. Komatsu;Hiroshi Ishida;T. Igaki;Jun K. Yamashita;K. Doi;Tae Hwa Chun;T. Yoshimasa;I. Tanaka;K. Nakao
中科院分区：
文献类型：
--
作者：
S. Suga;H. Itoh;Y. Komatsu;Hiroshi Ishida;T. Igaki;Jun K. Yamashita;K. Doi;Tae Hwa Chun;T. Yoshimasa;I. Tanaka;K. Nakao
我们证明了C型利钠肽(CNP)是利钠肽家族的第三个成员，并受包括肿瘤坏死因子-α在内的细胞因子的调节。因此，我们认为CNP作为一种内皮衍生的舒张肽，可以控制血管的张力和生长。我们还发现感染性休克患者血浆CNP浓度显著升高，其中肿瘤坏死因子α起重要作用。鉴于内皮细胞和单核巨噬细胞之间的相互作用在动脉粥样硬化的发病机制中起着关键作用，我们研究了内皮细胞和巨噬细胞共培养对内皮细胞产生CNP的影响。我们使用了人单核细胞白血病细胞系THP-1，当佛波醇12-肉豆蔻酸酯13-醋酸酯处理时，它会分化为巨噬细胞。EC与THP-1来源的巨噬细胞共培养比单独培养EC或EC与THP-1共培养而不经佛波酯处理时，CNP的分泌增加10倍以上。阻止EC与THP-1来源的巨噬细胞直接接触并不能减弱CNP分泌的增加。Northern blotting显示，共培养的EC中CNP信使RNA表达增强。我们从EC和THP-1来源的巨噬细胞共培养的条件培养液中检测到了肿瘤坏死因子α。此外，抗肿瘤坏死因子α抗体可抑制共培养细胞对CNP分泌的刺激。1 nM的CNP不能刺激EC或THP-1诱导的巨噬细胞产生cGMP，但能显著增加血管平滑肌细胞cGMP的产生。这些结果表明，THP-1来源的巨噬细胞在共培养过程中释放的肿瘤坏死因子α主要刺激内皮细胞产生CNP。内皮CNP水平升高可能是血管平滑肌细胞产生cGMP，调节局部血管张力和生长的血管介质之一，提示内皮CNP在动脉粥样硬化中的潜在意义。
We demonstrated endothelial production of C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, and its regulation by cytokines, including tumor necrosis factor-alpha (TNF alpha). We thus proposed that CNP can control vascular tone and growth as an endothelium-derived relaxing peptide. We also revealed the marked elevation of plasma CNP concentration in patients with septic shock, in which TNF alpha plays a significant part. As the interaction between endothelial cells (EC) and monocytes-macrophages plays a pivotal role in the pathogenesis of atherosclerosis, we investigated the effect of coculture of EC and macrophages on endothelial production of CNP. We used a human monocytic leukemia cell line, THP-1, which differentiates into macrophages when treated with phorbol 12-myristate 13-acetate. The coculture of EC and THP-1-derived macrophages enhanced CNP secretion by more than 10-fold compared with the single culture of EC or the coculture of EC and THP-1 without phorbol 12-myristate 13-acetate treatment. Prevention of direct contact between EC and THP-1-derived macrophages did not attenuate the increase in CNP secretion. Northern blotting revealed the augmentation of CNP messenger RNA expression in EC in the coculture. We detected TNF alpha in the conditioned medium from the coculture of EC and THP-1-derived macrophages. Furthermore, anti-TNF alpha antibody inhibited the stimulation of CNP secretion in the coculture. CNP at a concentration of 1 nM did not stimulate cGMP production in EC or THP-1-derived macrophages, but it elevated cGMP production significantly in vascular smooth muscle cells. These results indicate that endothelial production of CNP is stimulated mainly by TNF alpha released from THP-1-derived macrophages in the coculture. Endothelial CNP at the enhanced level may be one of the vascular mediators to regulate local vascular tone and growth through cGMP production by vascular smooth muscle cells, suggesting the potential significance of endothelial CNP in atherosclerosis.