Heme oxygenase-1 production by peripheral blood monocytes during acute inflammatory illnesses of children
Heme oxygenase-1 production by peripheral blood monocytes during acute inflammatory illnesses of children
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DOI：
10.1177/15353702-0322805-26
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发表时间：
2003-05-01
影响因子：
3.2
通讯作者：
Koizumi, S
中科院分区：
文献类型：
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作者：
Yachie, A;Toma, T;Koizumi, S
单核细胞在先天性和适应性抗原特异性免疫中发挥关键作用，它们构成免疫反应的关键组成部分。尽管大多数单核细胞衍生的细胞因子在体内表现出促炎功能，但血红素加氧酶-1 (HO-1)（一种诱导型血红素降解酶）通过产生一氧化碳和胆红素发挥有效的抗炎作用。我们比较了各种急性炎症性疾病和正常对照体内单核细胞产生的 HO-1。免疫组织化学检测发现，新鲜分离的单核细胞几乎不产生 HO-1，但在体外受到刺激后会迅速诱导产生。单核细胞产生的 HO-1 具有选择性，因为它不会在其他白细胞群（包括粒细胞和淋巴细胞）中被诱导。通过流式细胞术、免疫组织化学和逆转录聚合酶链反应检测，来自急性炎症性疾病（例如川崎病和急性传染病、病毒或细菌）的单核细胞产生显着水平的 HO-1。通过实时聚合酶链式反应对 HO-1 mRNA 表达进行定量分析，结果显示，对照组的单核细胞表现出较低但显着水平的 HO-1 mRNA，表明循环单核细胞不断产生 HO-1，以应对每天遇到的基础水平的氧化应激。在急性炎症性疾病中观察到的 HO-1 mRNA 水平显着升高表明，单核细胞产生的 HO-1 可作为有效的抗炎剂，在氧化应激和细胞因子血症存在的情况下控制过度的细胞或组织损伤。
Monocytes play key roles both in innate and adaptive antigen-specific immunity and they constitute critical components of the immune responses. Although most of the monocyte-derived cytokines exhibit proinflammatory functions in vivo, heme oxygenase-1 (HO-1), an inducible heme-degrading enzyme, exerts potent anti-inflammatory effect through production of carbon monoxide and bilirubin. We compared HO-1 production by monocytes in vivo in various acute inflammatory illnesses and in normal controls. Freshly isolated monocytes produced little HO-1 as detected by immunohistochemistry, but it was rapidly induced in vitro upon stimulation. HO-1 production by mono cytes was selective because it was not induced in other leukocyte populations, including granulocytes and lymphocytes. Monocytes from acute inflammatory illnesses, such as Kawasaki disease and acute infectious diseases, viral or bacterial, produced significant levels of HO-1, as detected by flow cytometry, immunohistochemistry, and reverse transcription polymerase chain reaction. Quantitative analysis of HO-1 mRNA expression by real-time polymerase chain reaction revealed that monocytes from controls exhibited low, but significant levels of HO-1 mRNA, indicating that circulating monocytes produce HO-1 constantly, in response to basal level of oxidative stress encountered daily. Significantly elevated HO-1 mRNA levels seen in acute inflammatory illnesses suggest that monocyte HO-1 production serve as potent anti-inflammatory agent to control excessive cell or tissue injury in the presence of oxidative stress and cytokinemia.