Enhanced expression of intracellular heme oxygenase-1 in deactivated monocytes from patients with severe systemic inflammatory response syndrome
Enhanced expression of intracellular heme oxygenase-1 in deactivated monocytes from patients with severe systemic inflammatory response syndrome
复制标题
DOI：
10.1097/01.ta.0000238228.67894.d7
复制
发表时间：
2006-09-01
影响因子：
--
通讯作者：
Sugimoto, Hisashi
中科院分区：
文献类型：
--
作者：
Mohri, Tomoyoshi;Ogura, Hiroshi;Sugimoto, Hisashi
背景：单核细胞失活是危重病患者感染易感性的重要因素。然而，单核细胞失活的机制尚未完全阐明。最近研究发现，细胞内血红素氧合酶-1(HO-1)是一种抗炎热休克蛋白，可被Toll样受体(TLRs)激活，并抑制炎症细胞因子的产生，如肿瘤坏死因子-α。在本研究中，我们评估了严重全身炎症反应综合征(SIRS)患者单核细胞内HO-1和TLRs的表达，并探讨了HO-1在单核细胞失活中的作用。SIRS的原因为脓毒症16例，创伤7例，其他4例。采用流式细胞仪检测外周血单核细胞表面HO-1、表面TLR2、TLR4、细胞内细胞因子的表达及TLR活化刺激的肿瘤坏死因子-α、白介素6的表达。用患者血清刺激正常单核细胞，检测细胞内HO-1的表达。同时检测血清细胞因子水平。结果：荧光显微镜下可清晰检测到细胞质HO-1。重度SIRS患者单核细胞HO-1、TLR2和TLR4的表达明显高于正常对照组，而含肽聚糖的患者单核细胞内肿瘤坏死因子-α的表达显著低于正常对照组(P<0.05)。患者血清刺激的正常单核细胞HO-1表达明显增强。结论：SIRS患者单核细胞内HO-1和TLRs的表达增强。细胞内HO-1对血清因子的反应增加可能在全身炎症后单核细胞失活中起作用。
Background: Monocyte deactivation is an important contributor to infectious susceptibility in critically ill patients. However, the mechanism of monocyte deactivation has not been fully elucidated. Recently, intracellular heme oxygenese-1 (HO-1), an anti-inflammatory heat-shock protein, was reported to be activated by Toll-like receptors (TLRs), and to inhibit inflammatory cytokine production such as that of TNF-alpha. In the present study, we evaluated the expression of intracellular HO-1 and TLRs in monocytes from patients with severe systemic inflammatory response syndrome (SIRS) and examined the role of HO-1 in monocyte deactivation.Patients: Twenty-seven patients who fulfilled the criteria for severe SIRS and had a serum C-reactive protein (CRP) level > 10 mg/dL were included in this study. The cause of SIRS was sepsis in 16 patients, trauma in 7, and other in 4. Expression of intracellular HO-1, surface TLR2 and TLR4, and intracellular cytokines; (TNF-alpha, Interleukin-6) stimulated via TLR activation were measured in circulating monocytes by flow cytometry. Intracellular HO-1 expression was evaluated in normal monocytes stimulated with patient serum. Serum cytokine levels were also measured. Patient data were compared with data from healthy volunteers (n = 16).Results: Cytoplasmic HO-1 was clearly detected by fluorescence microscopy. Expression of HO-1, TLR2, and TLR4 in monocytes was significantly enhanced in patients with severe SIRS compared with that in healthy volunteers, whereas intracellular TNF-alpha expression with peptidoglycan was significantly decreased (p < 0.05) in patients compared with that in healthy volunteers. HO-1 expression was significantly enhanced in normal monocytes stimulated with patient serum. Intracellular HO-1 levels were positively related to serum TNF-a levels in patients (r = 0.46).Conclusions: Expression of intracellular HO-1 and of TLRs was enhanced in deactivated monocytes from patients with SIRS. Increased production of intracellular HO-1 in response to serum factors may play a role in monocyte deactivation after systemic inflammation.