The pentraxins PTX3 and SAP in innate immunity, regulation of inflammation and tissue remodelling.
The pentraxins PTX3 and SAP in innate immunity, regulation of inflammation and tissue remodelling.
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DOI：
10.1016/j.jhep.2016.02.029
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发表时间：
2016-06
影响因子：
25.7
通讯作者：
Mantovani A
中科院分区：
文献类型：
--
作者：
Bottazzi B;Inforzato A;Messa M;Barbagallo M;Magrini E;Garlanda C;Mantovani A
五聚体是流体相模式识别分子的超家族，在进化过程中保守，具有环状多聚体结构的特征。C反应蛋白(CRP)和血清淀粉样蛋白P组分(SAP)构成了超家族的短五肽臂。CRP和SAP是在肝脏对IL-6作出反应时产生的，分别是人类和小鼠的急性期反应物。此外，SAP已被证明通过稳定所有类型的淀粉样纤维和调节单核细胞到纤维细胞的分化来影响组织重塑和纤维化。五角蛋白3(PTX3)是五角蛋白长臂的原型。基因靶向的小鼠和人类的遗传学和表观遗传学研究表明，PTX3在先天免疫和炎症以及组织重塑中发挥着基本的非多余作用。最近的研究揭示了PTX3作为外源性抑癌药的作用，可以调节癌症相关的炎症。此外，在酸性pH条件下，PTX3可与促进炎症基质重塑的临时基质成分相互作用。因此，组织修复过程中的酸化使PTX3处于组织重塑和修复模式，这表明基质和微生物识别是常见的、先天免疫的体液臂特征。
Pentraxins are a superfamily of fluid phase pattern recognition molecules conserved in evolution and characterized by a cyclic multimeric structure. C reactive protein (CRP) and serum amyloid P component (SAP) constitute the short pentraxin arm of the superfamily. CRP and SAP are produced in the liver in response to IL-6 and are acute phase reactants in humans and mice respectively. In addition SAP has been shown to affect tissue remodeling and fibrosis by stabilizing all types of amyloid fibrils and by regulating monocyte to fibrocyte differentiation. Pentraxin 3 (PTX3) is the prototype of the long pentraxin arm. Gene targeted mice and genetic and epigenetic studies in humans suggest that PTX3 plays essential non-redundant roles in innate immunity and inflammation as well as in tissue remodeling. Recent studies have revealed the role of PTX3 as extrinsic oncosuppressor able to tune cancer-related inflammation. In addition, at acidic pH PTX3 can interact with provisional matrix components promoting inflammatory matrix remodeling. Thus acidification during tissue repair sets PTX3 in a tissue remodeling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity.