Tumor necrosis factor/cachectin stimulates peritoneal macrophages, polymorphonuclear neutrophils, and vascular endothelial cells to synthesize and release platelet-activating factor.
Tumor necrosis factor/cachectin stimulates peritoneal macrophages, polymorphonuclear neutrophils, and vascular endothelial cells to synthesize and release platelet-activating factor.
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DOI：
10.1084/jem.166.5.1390
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发表时间：
1987-11-01
期刊：
影响因子：
--
通讯作者：
Baglioni C
中科院分区：
文献类型：
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作者：
Camussi G;Bussolino F;Salvidio G;Baglioni C
小鼠肿瘤坏死因子（mTNF）刺激培养的大鼠腹腔巨噬细胞产生血小板活化因子（PAF），其数量与用钙离子载体A23187或吞噬酶san治疗时形成的数量相当。释放到培养基中的细胞相关PAF与合成PAF相同，通过物理化学、色谱和酶分析确定。此外，巨噬细胞通过加入放射性前体如[3H]乙酰辅酶A或[3H]2-lyso-PAF来重新合成PAF。巨噬细胞与mTNF孵育4小时后，仅在治疗前1小时合成PAF。此时，细胞相关PAF的量大约等于释放到培养基中的PAF量。随后，细胞相关的PAF减少，而培养基中的PAF没有相应增加，这表明一些PAF正在降解。观察大鼠巨噬细胞对不同剂量mTNF和人TNF （hTNF）的反应。当mTNF浓度为10 ng/ml， hTNF浓度为50 ng/ml时，PAF的合成量最大。这一发现可能是由于hTNF对大鼠细胞TNF受体的亲和力较低。hTNF刺激脐带静脉培养的人血管内皮细胞产生PAF。PAF合成的时间过程比巨噬细胞慢，在处理后4 ~ 6 h达到最大值。当hTNF浓度为10 ng/ml时，PAF的合成效果最佳。内皮细胞合成的PAF只有20- 30%被释放到培养基中，即使经过几个小时的孵育。在大鼠多形核中性粒细胞中也检测到响应TNF的PAF合成，但在人肿瘤细胞和真皮成纤维细胞中未检测到。因此，PAF的产生是一种特殊的反应，在持续接受TNF治疗的巨噬细胞中是短暂的，并且似乎受到未知调节机制的控制。
Murine tumor necrosis factor (mTNF) stimulates production of platelet- activating factor (PAF) by cultured rat peritoneal macrophages in amounts comparable to those formed during treatment with the calcium ionophore A23187 or phagocytosis of zymosan. The cell-associated PAF that was released into the medium was identical to synthetic PAF, as determined with physicochemical, chromatographic, and enzymatic assays. Furthermore, de novo synthesis of PAF by macrophages was demonstrated by the incorporation of radioactive precursors such as [3H]acetyl- coenzyme A or [3H]2-lyso-PAF. Macrophages incubated with mTNF for 4 h synthesized PAF only during the first h of treatment. At this time, the amount of cell-associated PAF was approximately equal to that released into the medium. The cell-associated PAF decreased afterwards, whereas that in the medium did not correspondingly increase, suggesting that some PAF was being degraded. The response of rat macrophages to different doses of mTNF and human TNF (hTNF) was examined. Maximal synthesis of PAF was obtained with 10 ng/ml of mTNF and 50 ng/ml of hTNF. This finding may be explained by a lower affinity of hTNF for TNF receptors of rat cells. The hTNF stimulated production of PAF by human vascular endothelial cells cultured from the umbilical cord vein. The time course of PAF synthesis was slower than that observed with macrophages, with maximal production between 4 and 6 h of treatment. Optimal synthesis of PAF was obtained with 10 ng/ml of hTNF. Only 20- 30% of the PAF synthesized by endothelial cells was released into the medium, even after several hours of incubation. Synthesis of PAF in response to TNF was also detected in rat polymorphonuclear neutrophils, but not in human tumor cells and dermal fibroblasts. Therefore, production of PAF is a specialized response that is transient in macrophages continuously treated with TNF, and that appears to be controlled by unidentified regulatory mechanisms.