URATE CRYSTALS STIMULATE PRODUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA FROM HUMAN BLOOD MONOCYTES AND SYNOVIAL-CELLS - CYTOKINE MESSENGER-RNA AND PROTEIN KINETICS, AND CELLULAR-DISTRIBUTION
URATE CRYSTALS STIMULATE PRODUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA FROM HUMAN BLOOD MONOCYTES AND SYNOVIAL-CELLS - CYTOKINE MESSENGER-RNA AND PROTEIN KINETICS, AND CELLULAR-DISTRIBUTION
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DOI：
10.1172/jci115142
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发表时间：
1991-04-01
影响因子：
15.9
通讯作者：
DUFF, GW
中科院分区：
文献类型：
--
作者：
DIGIOVINE, FS;MALAWISTA, SE;DUFF, GW
尿酸盐（MSU）晶体为人血单核细胞产生肿瘤坏死因子（TNF）提供剂量依赖性刺激，TNF是一种具有促炎特性的细胞因子; TNF α单克隆抗体选择性抑制TNF活性。生物活性细胞相关的TNF活性在3 h达到峰值，并在6 h被细胞外活性超过，细胞外活性在12-18 h达到峰值。在免疫反应性TNF α中观察到相当的动力学。在用MSU晶体刺激的单核细胞中，TNF α mRNA积累在2-4 h时出现单峰，动力学与短半衰期转录物的快速产生相一致。相比之下，焦磷酸钙或羟基磷灰石晶体并不刺激TNF或messages.Fresh痛风石材料从痛风患者含有显着水平的TNF α和细胞培养痛风石产生TNF α在体外的显着生产。在类风湿性滑膜细胞中，TNF α的自发释放增加了体外暴露于MSU crystals. Take一起与早期的工作，这些结果支持痛风炎症的晶体刺激的细胞因子的生产提供了一个重要的晶体沉积和许多急性和慢性痛风性关节炎的临床和病理事实之间的联系的扩展视图。
Crystals of monosodium urate (MSU) provide a dose-dependent stimulus for the production by human blood monocytes of tumor necrosis factor (TNF), a cytokine with proinflammatory properties; TNF activity was inhibited selectively by monoclonal antibody to TNF alpha. Biologically active cell-associated TNF activity peaked at 3 h and was exceeded at 6 h by extracellular activity, which peaked at 12-18 h. Comparable kinetics were observed with immunoreactive TNF alpha. TNF alpha mRNA accumulation in monocytes stimulated with MSU crystals appeared as a single peak at 2-4 h, kinetics compatible with rapid production of a short half-life transcript. In contrast, crystals of calcium pyrophosphate or of hydroxyapatite did not stimulate significant production of TNF or of message.Fresh tophaceous material from a patient with gout contained significant levels of TNF alpha and cells cultured from the tophus produced TNF alpha in vitro. In rheumatoid synovial cells, spontaneous release of TNF alpha was increased by in vitro exposure to MSU crystals.Taken together with earlier work, these results support an expanded view of gouty inflammation in which the crystal-stimulated production of cytokines provides a crucial link between crystal deposition and many of the clinical and pathological facts of both acute and chronic gouty arthritis.