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[炎症中的急性期蛋白]

[Acute-phase proteins in inflammation].

作者信息

Engler R

机构信息

Laboratoire des Protéines de la Réaction inflammatoire, UFR Biomédicale des Saints-Pères, Paris.

出版信息

C R Seances Soc Biol Fil. 1995;189(4):563-78.

PMID:8564570
Abstract

The acute phase proteins (APPs) have been empirically defined as those whose plasma concentration changes following inflammatory reaction. Those proteins whose concentrations increase are referred to as positive APP, while those whose levels decline are termed negative APP. In man, positive APP are: alpha 1 acid glycoprotein, alpha 1 protease inhibitor, alpha 1 antichymotrypsin, haptoglobin, ceruloplasmin, fibrinogen, C-reactive protein, serum amyloid A. Great variability in the APP response between different species is observed. The principal functions of APP, result from the interaction of these proteins with ligands of various origins which give "protein-ligands" complexes. These complexes are cleared by the RES or by the hepatocyte. The results are protease inhibition, neutralization of toxic molecules such as hemoglobin or the superoxide anion, clearance of cell membranes and chromatin. The drop of the plasma concentration of negative APP during an inflammatory reaction carries a rise of free ligands (fatty acids, hormones, vitamins, trace elements). IL6 has been recognized as the principal regulator of most APP genes. The response of the hepatic cell to IL6 is characterized by the enhanced production of type 2 or IL6 specific APPs. The biochemical process of signal transduction is IL6--JAK2--APRF The set of APP genes regulated by IL1 type cytokines (type 1 APPs) is distinct from that regulated by IL6 type cytokine. IL1 and TNF alpha mediated stimulation of type 1 APP genes is synergistically enhanced by IL6 type cytokines. The biochemical process of signal transduction is IL1, IL6--Ras--MAP kinase--NFIL6 The targeted inflammatory proteic profile including the assay of C-reactive protein, haptoglobin and alpha 1 acid glycoprotein produces a "biological tool" to the clinician in order to manage an inflammatory response. IL6, a proteic marker for the future, connected with CRP, will be assayed during early inflammatory reaction.

摘要

急性期蛋白(APPs)根据经验被定义为血浆浓度在炎症反应后发生变化的蛋白质。浓度升高的那些蛋白质被称为阳性APP,而水平下降的则被称为阴性APP。在人类中,阳性APP包括:α1酸性糖蛋白、α1蛋白酶抑制剂、α1抗糜蛋白酶、触珠蛋白、铜蓝蛋白、纤维蛋白原、C反应蛋白、血清淀粉样蛋白A。不同物种之间APP反应存在很大差异。APP的主要功能源于这些蛋白质与各种来源的配体相互作用形成“蛋白质-配体”复合物。这些复合物由网状内皮系统(RES)或肝细胞清除。结果是蛋白酶抑制、中和诸如血红蛋白或超氧阴离子等有毒分子、清除细胞膜和染色质。炎症反应期间阴性APP血浆浓度的下降伴随着游离配体(脂肪酸、激素、维生素、微量元素)的增加。白细胞介素6(IL6)已被公认为大多数APP基因的主要调节因子。肝细胞对IL6的反应特征是2型或IL6特异性APP产量增加。信号转导的生化过程是IL6--Janus激酶2(JAK2)--急性淋巴细胞白血病1蛋白(APRF)。由IL1型细胞因子调节的APP基因集(1型APP)与由IL6型细胞因子调节的不同。IL1和肿瘤坏死因子α(TNFα)介导的1型APP基因刺激被IL6型细胞因子协同增强。信号转导的生化过程是IL1、IL6--Ras--丝裂原活化蛋白激酶(MAP激酶)--核因子IL6(NFIL6)。包括C反应蛋白、触珠蛋白和α1酸性糖蛋白检测在内的靶向炎症蛋白谱为临床医生管理炎症反应提供了一种“生物学工具”。IL6作为一种与C反应蛋白相关的未来蛋白质标志物,将在早期炎症反应期间进行检测。

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