DIFFERENTIAL-EFFECTS OF HEMORRHAGE ON KUPFFER CELLS - DECREASED ANTIGEN PRESENTATION DESPITE INCREASED INFLAMMATORY CYTOKINE (IL-1, IL-6 AND TNF) RELEASE
DIFFERENTIAL-EFFECTS OF HEMORRHAGE ON KUPFFER CELLS - DECREASED ANTIGEN PRESENTATION DESPITE INCREASED INFLAMMATORY CYTOKINE (IL-1, IL-6 AND TNF) RELEASE
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DOI：
10.1016/1043-4666(92)90039-t
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发表时间：
1992-01-01
期刊：
影响因子：
3.8
通讯作者：
CHAUDRY, IH
中科院分区：
文献类型：
--
作者：
AYALA, A;PERRIN, MM;CHAUDRY, IH
尽管研究表明单纯出血诱导细胞介导的免疫的深度抑制并增强宿主对脓毒症的易感性，但其机制仍不清楚。由于库普弗细胞（KC）的位置有恒定的暴露于各种免疫调节剂和低血压过程中释放的抗原，我们已经研究了抗原呈递KC，在引发抗原特异性免疫反应或与之相关的过程中的关键组成部分，是否被抑制出血后。将C3 H/HeN小鼠流血的至平均BP 35 mmHg并维持60 min，然后用其自身血液和足够的液体复苏。在出血后的不同时间段处死小鼠以从肝脏获得KC，并评估它们将抗原呈递给致敏克隆Th/细胞系（D10.G4.1）的能力。出血的小鼠表现出抗原呈递能力的显著降低，从出血后2小时开始并持续长达3-5天。KC表达小鼠白细胞介素1（mIL-1）的能力在出血后2 h显著下降，但在出血后24 h这种作用不明显。相比之下，KC产生IL-1，IL-6和肿瘤坏死因子（TNF）（细胞因子，可以共刺激T细胞抗原呈递）的能力显着增强，在第一个24小时出血后。观察到出血后至少持续3天的每个KC的平均荧光的平均值和Ia抗原阳性KC的百分比均显著降低。布洛芬（一种环氧合酶阻断剂）能够部分恢复体外老化小鼠KC的抗原提呈能力，表明布洛芬参与了这种功能障碍。因此，KC抗原呈递的抑制，以及这些细胞释放可能产生细胞和器官功能障碍的炎性介质（TNF、IL-1、IL-6和前列腺素类）的能力增强，可能有助于宿主对出血后脓毒症的易感性增强。
Although studies indicate that simple hemorrhage induces profound depression of cell-mediated immunity and enhances the host's susceptibility to sepsis, the mechanism for this remains unknown. Since the Kupffer cells (KC) are positioned to have constant exposure to various immunomodulators and antigens released during hypotension, we have examined whether antigen presentation by KC, a critical component in eliciting an antigen specific immune response or those processes associated with it, are depressed following hemorrhage. C3H/HeN mice were bled to and maintained at a mean BP of 35 mmHg for 60 min, and then resuscitated with their own blood and adequate fluids. The mice were killed at varying periods of time after hemorrhage to obtain KC from the liver, and assessed for their capacity to present antigen to a sensitized clone Th/cell line (D10.G4.1). Hemorrhaged mice exhibited a marked decrease in antigen presenting capacity beginning as little as 2 h and lasting up to 3–5 days post-hemorrhage. The ability of KC to express mouse interleukin 1 (mIL-1) showed a significant decline at 2 h following hemorrhage, but this effect was not apparent at 24 h post-hemorrhage. In contrast, KC capacity to produce IL-1, IL-6 and tumour necrosis factor (TNF) (cytokines which can co-stimulate T cell antigen presentation) was markedly enhanced during the first 24 h following hemorrhage. A marked decrease was observed in both the mean of the average fluorescence per KC and the percent of Ia antigen-positive KC which persisted for at least 3 days after hemorrhage. The ability of ibuprofen (a cyclooxygenase blocker) to partially restore the antigen presenting capacity of KC from hemorrhaged mice in vitro indicates that prostaglandins are involved in this dysfunction. Thus, the depression of KC antigen presentation, as well as the enhanced capacity of these cells to release inflammatory mediators (TNF, IL-1, IL-6 and prostanoids) which may produce cell and organ dysfunction, could contribute to the host's enhanced susceptibility to sepsis following hemorrhage.