Carbon dioxide differentially affects the cytokine release of macrophage subpopulations exclusively via alteration of extracellular pH
Carbon dioxide differentially affects the cytokine release of macrophage subpopulations exclusively via alteration of extracellular pH
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DOI：
10.1007/s00464-004-2175-6
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发表时间：
2006-04-01
影响因子：
3.1
通讯作者：
Ure, BM
中科院分区：
文献类型：
--
作者：
Kos, M;Kuebler, JF;Ure, BM
背景：内窥镜手术后预后的改善归因于较少的手术创伤。然而，潜在的机制尚未完全理解，并且已经假定用于气腹、细胞酸化和/或缺乏空气污染的CO的直接作用在内窥镜手术期间另外调节免疫功能。我们研究了CO，培养，胞外酸化的影响。方法：采用大鼠巨噬细胞系R2和NR 8383，观察空气污染对两种不同巨噬细胞群炎症反应的影响。在这些实验组中测定脂多糖（LPS）刺激后的白细胞介素-6（IL-6）和一氧化氮：在100%CO2、5%CO2和室内空气中孵育2小时;在5%CO2中在pH 7.4、6.5和5.5下孵育2小时;在100%CO2中孵育。5%CO2和室内空气，固定pH值6.3。在孵育期间监测细胞外pH。结果：100%CO_2孵育时，细胞外pH值下降到6.3。NR 8383细胞经CO2孵育后IL-6的释放减少，而R2细胞则增加（p < 0.05）。空气孵育不改变其活性。将细胞外pH降低至6.5模拟了CO2的作用，并且降低至5.5抑制了两种细胞系中的IL-6释放。在固定pH值为6.3时，CO2和空气孵育没有影响。CO2和pH值对一氧化氮的释放和活力没有影响。细胞内pH值降低与细胞外酸化没有显着差异两个cellline.Conclusions：在CO2中孵育过程中细胞外pH值的降低差异影响巨噬细胞亚群中IL-6的释放。这可能解释了文献中相互矛盾的结果。此外，我们证明了空气污染不影响巨噬细胞细胞因子的释放。细胞外pH的降低是CO2孵育后巨噬细胞细胞因子释放改变的主要潜在机制，并且似乎维持细胞内pH的能力不由CO2或细胞外酸化的影响决定。
Background: The improved Outcome after endoscopic surgery has been attributed to less surgical trauma. However, the underlying mechanisms are not fully understood, and direct effects of CO, used for pneumo-peritoneum, cellular acidification, and/or the lack of air contamination have been postulated to additionally modulate immune functions during endoscopic surgery. We investigated the effects of CO, incubation, extracellular acidification. and air contamination on the inflammatory response of two distinct macrophage populations.Methods: R2 and NR 8383 rat macrophage cell lines were used. Interleukin-6 (IL-6) and nitric oxide after lipopolysaccharide (LPS) stimulation were determined in these sets of experiments: incubation in 100% CO2, 5% CO2, and room air for 2h; incubation at pH 7.4, 6.5, and 5.5 for 2 h in 5% CO2; and incubation in 100% CO2. 5% CO2 and room air in fixed pH 6.3. The extracellular pH was monitored during incubation. We determined the alteration of intracellular pH in cells subjected to extracellular acidification by fluorescence microscopy.Results: Extracellular pH decreased to 6.3 during 100% CO2 incubation. IL-6 release was reduced after CO2 incubation in NR 8383 cells and increased in R2 cells (p < 0.05). It was not altered by air incubation. Decreasing the extracellular pH to 6.5 mimicked the effects of CO2 and a decrease to 5.5 suppressed IL-6 release in both cell lines. In fixed pH at 6.3, CO2 and air incubation had no effect. CO2 and pH had no impact on nitric oxide release and vitality. Intracellular pH decreased with extracellular acidification without significant difference between the two cell lines.Conclusions: A decrease in extracellular pH during incubation in CO2 differentially affects IL-6 release in macrophage subpopulations. This may explain contradictory results in the literature. Moreover, we demonstrated that air contamination does not affect macrophage cytokine release. The decrease in extracellular pH is the primary underlying mechanism of the alteration of macrophage cytokine release after CO2 incubation, and it appears that the ability to maintain intracellular pH is not determined by the effects of CO2 or extracellular acidification.