Endothelins, peptides with potent vasoactive properties, are produced by human macrophages.
Endothelins, peptides with potent vasoactive properties, are produced by human macrophages.
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DOI：
10.1084/jem.172.6.1741
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发表时间：
1990-12-01
期刊：
影响因子：
--
通讯作者：
Fauci AS
中科院分区：
文献类型：
--
作者：
Ehrenreich H;Anderson RW;Fox CH;Rieckmann P;Hoffman GS;Travis WD;Coligan JE;Kehrl JH;Fauci AS
内皮素是一种多肽，最初从内皮细胞中分离出来，具有强大的血管活性和有丝分裂特性。在这项研究中，我们证明了人巨噬细胞合成和分泌内皮素。免疫细胞化学法检测培养的人巨噬细胞内皮素1和内皮素3阳性。它们产生和释放这些肽的能力被反相高效液相色谱和放射免疫测定相结合证实，分别针对内皮素1和3。在细胞提取物和巨噬细胞条件培养基中均鉴定出免疫反应肽。脂多糖或肉豆蔻酸酯（PMA）可刺激巨噬细胞分泌内皮素1，而非内皮素3。使用内皮素1 cDNA探针对巨噬细胞总RNA进行Northern blot分析，发现pma处理的巨噬细胞中内皮素mRNA被诱导。此外，免疫反应性内皮素1和3在人单核细胞U937细胞和新分离的人单核细胞中被发现。相比之下，在人中性粒细胞和淋巴细胞的细胞提取物中未检测到免疫反应性内皮素。用免疫组织化学方法在人肺石蜡切片上观察组织巨噬细胞内皮素的表达。总之，人类巨噬细胞产生内皮素的发现表明这些肽在组织巨噬细胞的微环境中起重要作用。巨噬细胞来源的内皮素可能在血管生理学中具有重要功能，异常产生可能导致血管病理。
Endothelins are peptides, originally isolated from endothelial cells, with potent vasoactive and mitogenic properties. In this study, we demonstrate that human macrophages synthesize and secrete endothelins. Cultured human macrophages were found by immunocytochemistry to stain positively for endothelin 1 and endothelin 3. Their capability to produce and release these peptides was confirmed by a combination of reverse-phase high-performance liquid chromatography and radioimmunoassays, specific for endothelin 1 and 3, respectively. Immunoreactive peptides were identified both in cellular extracts and in macrophage-conditioned medium. The secretion of endothelin 1, but not of endothelin 3, from macrophages could be stimulated 6-10-fold by lipopolysaccharide or phorbol myristate acetate (PMA). Northern blot analysis of total macrophage RNA using an endothelin 1 cDNA probe revealed induction of endothelin mRNA in PMA-treated macrophages. Furthermore, immunoreactive endothelin 1 and 3 were found in U937 cells, a human promonocytic line, and in freshly isolated human monocytes. In contrast, no immunoreactive endothelin was detected in cell extracts from human neutrophils and lymphocytes. The expression of endothelins in tissue macrophages was demonstrated in paraffin sections of human lung using immunohistochemistry. In conclusion, the finding that human macrophages produce endothelins suggests an important role for these peptides in the microenvironment of tissue macrophages. Macrophage-derived endothelins may have an essential function in blood vessel physiology, and aberrant production may contribute to vessel pathology.