HYPOXIA INDUCES A HUMAN MACROPHAGE CELL-LINE TO RELEASE TUMOR-NECROSIS-FACTOR-ALPHA AND ITS SOLUBLE RECEPTORS IN-VITRO
HYPOXIA INDUCES A HUMAN MACROPHAGE CELL-LINE TO RELEASE TUMOR-NECROSIS-FACTOR-ALPHA AND ITS SOLUBLE RECEPTORS IN-VITRO
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DOI：
10.1006/jsre.1993.1044
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发表时间：
1993-04-01
影响因子：
2.2
通讯作者：
GRANGER, GA
中科院分区：
文献类型：
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作者：
SCANNELL, G;WAXMAN, K;GRANGER, GA
出血和创伤后的组织缺氧可能是休克后全身炎症反应的起始因素。本文研究了缺氧对人单核细胞系（THP-1）体外释放肿瘤坏死因子α（TNFα）及其可溶性膜受体（TNFαR）的作用。将含有500，000 THP-1细胞/ml的平底板置于气密密封盒中，暴露于缺氧（O2= 1%）或对照（O2= 9%）长达24小时。通过ELISA检测上清液中的TNFα以及TNFα的55和75 kDa可溶性受体。通过活体染料摄取评估细胞活力，发现在整个低氧暴露过程中细胞活力得以维持。培养基pH值水平在正常范围内。在一式两份进行的8项实验中，对照样品在24小时内发生了最小变化。对照组平均值和SD为：TNFα = 12.0 ± 4.2，55-kDa R = 34.6 ± 2.03，75-kDa R = 38.88 ± 9.68 pg/ml。在缺氧过程中，TNFα早在暴露的前30分钟（41.3 ± 2.3 pg/ml）释放，在1小时（52 ± 5.0 pg/ml）时有一个小的峰值，在18小时（526 ± 48 pg/ml）时有一个更明显的峰值。55-和75-kDa的R释放的缺氧单核细胞，释放是渐进的，在这项研究中，在24小时最大。55-kDa R的最大释放值为236 ± 15 pg/ml，而75-kDa R的最大释放值为2450 ± 63 pg/ml。通过单因素方差分析，然后进行Student-Newman-Keuls检验进行多重比较，除15分钟时间段外，P值均<0.01，其中P> 0.05。我们的结论是，当暴露于完全或几乎完全缺氧时，人单核细胞自发释放TNFα，随后释放TNFαR。
Tissue hypoxia following hemorrhage and trauma is a possible initiating factor of the generalized inflammatory response seen after shock. The role of hypoxia in the release from a human monocyte cell line (THP-1) of tumor necrosis factor-α (TNFα) and its soluble membrane receptors (TNFαR)in-vitrois investigated in this study. Flat-bottom plates with 500,000 THP-1 cells/ml were placed in air-tight sealed boxes and exposed to hypoxia (O2= 1%) or controls (O2= 9%) for up to 24 hr. Supernatants were tested for TNFα, as well as 55- and 75-kDa soluble receptors for TNFα, by ELISA. Cell viability was assessed by vital dye uptake and was found to be maintained throughout hypoxic exposure. Medium pH levels were within normal range. In eight experiments conducted in duplicate, minimal change over 24 hr occurred in control samples. Control mean and SD were: TNFα = 12.0 ± 4.2, 55-kDa R = 34.6 ± 2.03, and 75-kDa R = 38.88 ± 9.68 pg/ml. During hypoxia, TNFα was released as early as the first 30 min of exposure (41.3 ± 2.3 pg/ml) with a small peak at 1 hr (52 ± 5.0 pg/ml) and a later more pronounced peak at 18 hr (526 ± 48 pg/ml). Both 55- and 75-kDa R were released by the hypoxic monocytes; release was progressive and was maximal at 24 hr in this study. Maximal release value of 55-kDa R was 236 ± 15 pg/ml, while for 75-kDa R it was 2450 ± 63 pg/ml. By one-way analysis of variance followed by the Student-Newman-Keuls test for multiple comparisons,Pvalues were <0.01 at all but the 15-min time period, whereP> 0.05. We conclude that when exposed to complete or nearly complete absence of oxygen, human monocytes spontaneously release TNFα, followed by TNFαR.