Immune response to severe insults: reaction through Toll-like receptors

我们研究的目的如下。(1)阐明脓毒症或创伤患者对严重损伤（如toll样受体反应性）的免疫反应。(2)评价严重损伤后参与免疫反应和炎症反应的细胞功能变化。在本研究中，我们发现了以下结果：(1)单核细胞功能：严重SIRS患者单核细胞中toll样受体2、4和细胞内血红素加氧酶-1的表达均增强。通过toll样受体产生的细胞内细胞因子在患者中被抑制。在患者血清刺激下，健康志愿者单核细胞血红素加氧酶-1表达增强。这些结果提示血红素加氧酶-1在单核细胞中的表达增强在单核细胞失活中起作用。(2)多形核白细胞（PMNL）功能：SIRS患者PMNL中NF-kB和糖皮质激素受体的核内表达明显增强。这两个转录因子之间有很强的相关性。NF-kB和糖皮质激素受体之间的表达平衡可能调节严重损伤后PMNL的激活和炎症反应。活化的PMNLs增强了微颗粒的产生，增加了内皮细胞的粘附分子。另一方面，活化的PMNLs增强了肝细胞生长因子的分泌，这支持了PMNLs在严重损伤后组织修复中的重要作用。(3)血管内皮功能：严重SIRS患者循环血液中内皮源性微粒明显增加，微粒与活化PMNLs的结合增强。这些结果表明，PMNLs与内皮细胞之间的相互作用可能在严重损伤后的炎症反应中起重要作用。(4) γ - δ t细胞功能：严重SIRS患者循环血液中γ - δ t细胞明显活化和减少。γ - δ t细胞可能在严重损伤后的宿主先天免疫中起关键作用。少

The objective of our study was as follows. (1) To clarify the immune response to severe insults (such as Toll-like receptor reactivity) in patients with sepsis or trauma. (2) To evaluate the functional changes in cells, which participate in immune reaction and inflammatory response after severe insults.We found the following results in the present study.(1)Monocyte functions: The expression of Toll-like receptor 2 amd 4, and intracellular heme oxygenase-1 were both enhanced in monocytes from patients with severe SIRS. The intracellular cytokine produnction through Toll-like receptors was inhibited in the patients. The heme oxygenase-1 expression in monocytes from healthy volunteers was enhanced when stimulated with the patients' serum. These results suggest that the enhanced expression of heme oxygenase-1 in monocytes plays a role in monocyte deactivation. (2) Polymorphonuclear leukocyte (PMNL) functions: The intranuclear expressions of NF-kB and glucocorticoid receptor in PMNLs were s … More ignificantly enhanced in SIRS patients. There was a strong correlation between these two transcriptional factors. The balance between expression of NF-kB and glucocorticoid receptors may regulate the PMNL activation and inflammatory response following severe insults. Activated PMNLs enhanced the production of microparticles with increased adhesion molecules to endothelium. On the other hand, activated PMNLs enhanced the secretion of hepatocyte growth factor, which supports the significant role of PMNLs in tissue repair following severe insults. (3) Vascular endothelial functions : Endothelium-derived microparticles in circulating blood were significantly increased in patients with severe SIRS, and the binding of microparticles to the activated PMNLs was enhanced. These results showed that the interaction between PMNLs and emdothelium may play an important role in inflammatory response following severe insults. (4) Gamma-delta T-cell functions : Gamma-delta T-cells were significantly activated and decreased in the circulating blood in patients with severe SIRS. Gamma-delta T-cells may play a key role in host innate immunity following severe insults. Less