RECOMBINANT HUMAN TNF INDUCES PRODUCTION OF GRANULOCYTE MONOCYTE COLONY-STIMULATING FACTOR
RECOMBINANT HUMAN TNF INDUCES PRODUCTION OF GRANULOCYTE MONOCYTE COLONY-STIMULATING FACTOR
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DOI：
10.1038/323079a0
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发表时间：
1986-09-04
期刊：
影响因子：
64.8
通讯作者：
KOEFFLER, HP
中科院分区：
文献类型：
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作者：
MUNKER, R;GASSON, J;KOEFFLER, HP
肿瘤坏死因子（TNF）由暴露于内毒素的巨噬细胞合成1。它在小鼠中产生多种肿瘤的出血性坏死，并且在体外对各种转化细胞系具有细胞抑制或细胞杀灭作用，但正常人或啮齿动物细胞的活力不受影响2 -4。TNF的作用不太可能仅限于肿瘤的排斥。集落刺激因子（CSF）是造血祖细胞存活、增殖和分化所必需的。称为粒细胞-单核细胞集落刺激因子（GM-CSF）的造血生长因子具有刺激正常粒细胞-单核细胞和嗜酸性粒细胞干细胞的增殖和分化以及增强多能、巨核细胞和红系干细胞的增殖的能力5。此外，GM-CSF刺激成熟粒细胞和巨噬细胞中的多种功能活性，例如抑制迁移、微生物吞噬、氧化代谢和肿瘤细胞的抗体依赖性细胞毒性杀伤5 -7。我们在这里表明，TNF显着刺激生产的GM-CSF信使RNA和蛋白质在正常人肺成纤维细胞和血管内皮细胞，并在几个恶性组织的细胞。
Tumour necrosis factor (TNF) is synthesized by macrophages exposed to endotoxin1. It produces haemorrhagic necrosis of a variety of tumours in mice and is cytostatic or cytocidal against various transformed cell linesin vitro, but viability of normal human or rodent cells is unaffected2–4. The role of TNF is unlikely to be restricted to the rejection of tumours. Colony-stimulating factors (CSFs) are required for survival, proliferation and differentiation of haematopoietic progenitor cells. The haematopoietic growth factor known as granulocyte-monocyte colony-stimulating factor (GM-CSF) has the ability to stimulate proliferation and differentiation of normal granulocyte-monocyte and eosinophil stem cells and enhance the proliferation of pluripotent, megakaryocyte and erythroid stem cells5. In addition, GM-CSF stimulates a variety of functional activities in mature granulocytes and macrophages, for example inhibition of migration, phagocytosis of microbes, oxidative metabolism, and antibody-dependent cytotoxic killing of tumour cells5–7. We show here that TNF markedly stimulates production of GM-CSF messenger RNA and protein in normal human lung fibroblasts and vascular endothelial cells, and in cells of several malignant tissues.