Vascular endothelial cells and granulopoiesis: interleukin-1 stimulates release of G-CSF and GM-CSF.
Vascular endothelial cells and granulopoiesis: interleukin-1 stimulates release of G-CSF and GM-CSF.
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DOI：
10.1182/blood.v71.1.99.bloodjournal71199
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发表时间：
1988
期刊：
影响因子：
20.3
通讯作者：
K. Zsebo;Vn Yuschenkoff;S. Schiffer;D. Chang;E. McCall;C. Dinarello;Mallory Brown;B. Altrock;G. Bagby
中科院分区：
文献类型：
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作者：
K. Zsebo;Vn Yuschenkoff;S. Schiffer;D. Chang;E. McCall;C. Dinarello;Mallory Brown;B. Altrock;G. Bagby
培养的单核巨噬细胞产生可溶性因子，刺激内皮细胞释放GM-CsA。最近发现的一个这样的因子是白介素1(IL1)。研究旨在确定IL-1刺激的内皮细胞释放哪些类型的造粒细胞因子。在含有IL-1α和β的培养液中培养3d的内皮细胞上清液进行小鼠和人CFU-GM集落生长实验。并检测了条件培养液对WEHI-3B粒-单核细胞白血病细胞分化的影响。单独含有IL-1的对照培养液或未刺激的内皮细胞条件培养液在任何生物检测中都不含有可检测到的CsA。经IL-1刺激的内皮细胞条件培养液刺激人和小鼠CFU-GM克隆生长，并诱导WEHI-3B细胞向巨噬细胞分化。用高度特异的中和性G-CSF单抗处理这些条件培养液，可完全抑制它们在小鼠CFU-GM实验中的活性，但仅部分抑制人骨髓GM集落生长。用中和兔抗人GM-CSF抗体处理活性条件培养液，部分降低了人GM集落生长试验中的培养液活性。内皮细胞培养上清的G-CSF放射免疫分析和内皮细胞胞浆RNA的Northern印迹分析证实，IL-1诱导了G-CSF和GM-CSF基因的表达。由于用这两种抗体处理的培养液使人GM集落生长试验中的所有活性都丧失，我们得出结论：IL-1刺激的内皮细胞同时释放G和GM-CSF，这是这些细胞在体外释放的克隆形成试验中唯一能检测到的粒细胞因子。
Cultured mononuclear phagocytes produce soluble factors that stimulate endothelial cells to release GM-colony-stimulating activity (GM-CSA). One such factor was recently identified as interleukin 1 (IL 1). Studies were designed to determine which types of granulopoietic factors are released by IL 1-stimulated endothelial cells. Supernatants from endothelial cells cultured for 3 days in medium containing IL 1 alpha and beta were tested in both murine and human CFU-GM colony growth assays. The effect of conditioned media on differentiation of WEHI-3B myelomonocytic leukemic cells was also examined. Control media containing IL 1 alone or unstimulated endothelial cell-conditioned media contained no detectable CSA in any bioassay. Medium conditioned by IL 1-stimulated endothelial cells stimulated the clonal growth of both human and murine CFU-GM and induced macrophage differentiation of WEHI-3B cells. Treatment of these conditioned media with a highly specific neutralizing monoclonal G-CSF antibody completely inhibited their activity in the murine CFU-GM assay, but only partially inhibited GM colony growth by human marrow. Treatment of the active conditioned media with a neutralizing rabbit anti-human GM-CSF antibody partially reduced the activity of the media in the human GM-colony growth assay. G-CSF radioimmunoassay of endothelial cell culture supernatants and Northern blot analysis of endothelial cell cytoplasmic RNA for GM-CSF gene transcripts confirmed that IL 1 induced expression of both G-CSF and GM-CSF genes. Because treatment of media with both antibodies abrogated all activity in the human GM colony growth assay, we conclude that IL 1-stimulated endothelial cells release both G and GM-CSF and that these are the only granulopoietic factors detectable in clonogenic assays released by these cells in vitro.