The regulation of superoxide generation and nitric oxide synthesis by C‐reactive protein

The regulation of superoxide generation and nitric oxide synthesis by C‐reactive protein
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C反应蛋白对超氧化物生成和一氧化氮合成的调节

DOI:
10.1046/j.1365-2567.1998.00552.x
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发表时间:
1998
期刊:
影响因子:
6.4
通讯作者:
Mookerjea
Mookerjea
中科院分区:
医学2区
文献类型:
--
作者:
Ratnam;Mookerjea

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活化的巨噬细胞利用活性氧中间体和活性氧氮中间体来防御微生物。然而,同时产生的超氧化物(O− 2 stec)和一氧化氮(NO)可能会对宿主细胞有害,因为会产生过氧亚硝酸盐,二氧化氮和羟基自由基。 因此,调节这些分子的产生对宿主的存活至关重要。在炎症或感染期间,许多物种的血清C反应蛋白(CRP)水平升高。人和大鼠CRP已显示与吞噬细胞结合并相互作用。由于CRP的许多相互作用涉及与磷酸胆碱配体的结合,我们研究了CRP通过调节巨噬细胞中的磷脂酰胆碱(PC)代谢在O− 2代谢和NO生成中的作用。 这项研究表明,虽然大鼠CRP抑制佛波酯肉豆蔻酸酯乙酸酯(PMA)诱导的大鼠巨噬细胞释放O− 2 stec,但CRP处理的巨噬细胞以时间和剂量依赖性方式释放NO。 CRP增加诱导型一氧化氮合酶(iNOS)酶以及诱导型一氧化氮合酶mRNA水平在大鼠巨噬细胞。三环癸烷-9-基-黄原酸酯(D 609),一种PC磷脂酶C(PC-PLC)的抑制剂,抑制了iNOS的诱导,但增强了PMA诱导的O− 2 stec的释放。 这些数据表明,在炎症期间CRP水平升高可能导致巨噬细胞NADPH氧化酶和iNOS活性的差异调节。肝脏合成CRP的增加可能有助于吞噬细胞避免同时O− 2释放和NO合成的机制,这可能是通过PC‐PLC的调节介导的。 
Activated macrophages utilize both reactive oxygen intermediates and reactive oxynitrogen intermediates for defence against microbes. However, simultaneous generation of superoxide (O− 2˙) and nitric oxide (NO) could be harmful to host cells due to the production of peroxynitrite, nitrogen dioxide and hydroxyl radicals. Therefore, the regulation of the production of these molecules is critical to host survival. During periods of inflammation or infection, the level of serum C‐reactive protein (CRP) increases in many species. Human and rat CRP have been shown to bind and interact with phagocytic cells. Since many of the interactions of CRP involve the binding to the phosphocholine ligand, we studied the role of CRP in O− 2˙ and NO generation through the modulation of phosphatidylcholine (PC) metabolism in macrophages. This study has shown that, while rat CRP inhibited phorbol myristate acetate‐ (PMA) induced release of O− 2˙ by rat macrophages, CRP‐treated macrophages released NO in a time‐ and dose‐dependent manner. CRP increased inducible nitric oxide synthase (iNOS) enzyme as well as iNOS mRNA levels in rat macrophages. Tricyclodecan‐9‐yl‐xanthogenate (D609), an inhibitor to PC phospholipase C (PC‐PLC), suppressed iNOS induction but enhanced PMA‐induced release of O− 2˙. These data indicate that an increased level of CRP during periods of inflammation may result in differential regulation of macrophage NADPH oxidase and iNOS activity. Increased hepatic synthesis of CRP may contribute to the mechanism by which phagocytic cells avoid simultaneous O− 2˙ and NO synthesis, and this could possibly be mediated through the regulation of PC‐PLC.
DOI: --
发表时间: 1990
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
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通讯作者: Mortensen,RF
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发表时间: 1990-02-01
影响因子: 11.1
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DOI: --
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期刊: Cancer research
影响因子: 11.2
作者:
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DOI: 10.1016/0167-4889(91)90101-3
发表时间: 1991
期刊: Biochimica et biophysica acta
影响因子: --
作者:
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通讯作者: Mortensen,RF
DOI: 10.1126/science.1281928
发表时间: 1992-12-18
期刊: SCIENCE
影响因子: 56.9
作者:
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通讯作者: LOSCALZO, J