STIMULATION OF HUMAN MONOCYTE BETA-GLUCAN RECEPTORS BY GLUCAN PARTICLES INDUCES PRODUCTION OF TNF-ALPHA AND IL-1-BETA
STIMULATION OF HUMAN MONOCYTE BETA-GLUCAN RECEPTORS BY GLUCAN PARTICLES INDUCES PRODUCTION OF TNF-ALPHA AND IL-1-BETA
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DOI：
10.1016/0192-0561(92)90007-8
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发表时间：
1992-11-01
期刊：
影响因子：
--
通讯作者：
CZOP, JK
中科院分区：
文献类型：
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作者：
ABEL, G;CZOP, JK
β-葡聚糖是通过涉及巨噬细胞激活的机制快速增强宿主对多种生物损伤的抵抗力的药物。为了确定刺激人单核细胞上的 β-葡聚糖受体是否会导致细胞因子的产生，将单核细胞单层与纯化的酵母葡聚糖颗粒一起孵育，并测量肿瘤坏死因子-α (TNF-α) 和白介素-1β (IL-1β) mRNA 和蛋白质。通过 Northern 印迹分析，在与葡聚糖颗粒孵育 30 分钟内检测到 TNF-α mRNA，在 2 小时达到峰值，并在至少 8 小时内保持升高状态。 IL-1β mRNA 的葡聚糖诱导遵循相似的起始和积累时间过程。通过酶联免疫吸附测定 (ELISA)，1 小时内，葡聚糖处理的细胞上清液中出现显着水平的 TNF-α 和 IL-1β，并且两种细胞因子在 4 小时内达到平台水平。当颗粒与细胞的比例为 0.4 至 18 时，葡聚糖颗粒诱导 TNF-α 和 IL-1β mRNA 的剂量依赖性增加，以及 TNF-α 和 IL-1β 蛋白的相应增加。将单核细胞暴露于葡聚糖颗粒 0 - 30 分钟并洗涤，然后在无颗粒缓冲液中继续孵育 4 小时，以与吞噬作用相容的时间依赖性方式诱导 TNF-α 和 IL-1β 的产生和分泌。用胰蛋白酶预处理单核细胞单层以剂量依赖性方式减少葡聚糖诱导的TNF-α和IL-1β的产生，其中5μg/ml的胰蛋白酶可实现大于50%的减少。因此，葡聚糖颗粒通过依赖于胰蛋白酶敏感的β-葡聚糖受体的机制诱导人类单核细胞产生TNF-α和IL-1β，
Beta-glucans are pharmacologic agents that rapidly enhance host resistance to a variety of biologic insults through mechanisms involving macrophage activation. To determine whether stimulation of the beta-glucan receptors on human monocytes resulted in cytokine production, monolayers of monocytes were incubated with purified yeast glucan particles and measured for tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) mRNA and protein. By Northern blot analysis, TNF-alpha mRNA was detected within 30 min of incubation with glucan particles, peaked at 2 h, and remained elevated for at least 8 h. Glucan induction of IL-1beta mRNA followed a similar time-course of initiation and accumulation. By enzyme-linked immunosorbent assays (ELISAs), significant levels of TNF-alpha and IL-1beta were present in supernatants of glucan-treated cells within 1 h and plateau levels of both cytokines were approached within 4 h. At particle-to-cell ratios of from 0.4 to 18, glucan particles induced dose-dependent increases in TNF-alpha and IL-1beta mRNA and corresponding increases in TNF-alpha and IL-1beta proteins. Exposure of monocytes to glucan particles for 0 - 30 min and washing before continued incubation for 4 h in particle-free buffer induced production and secretion of TNF-alpha and IL-1beta in a time-dependent fashion compatible with phagocytosis. The pre-treatment of monocyte monolayers with trypsin reduced glucan-induced production of TNF-alpha and IL-1beta in a dose-dependent manner with 5 mug/ml of trypsin effecting reductions of greater than 50%. Thus, glucan particles induce human monocyte production of TNF-alpha and IL-1beta by a mechanism that is dependent on trypsin-sensitive beta-glucan receptors,