Role of complement and Fcγ receptors in the protective activity of the long pentraxin PTX3 against Aspergillus fumigatus
Role of complement and Fcγ receptors in the protective activity of the long pentraxin PTX3 against Aspergillus fumigatus
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DOI：
10.1182/blood-2009-12-258376
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发表时间：
2010-12-09
期刊：
影响因子：
20.3
通讯作者：
Garlanda, Cecilia
中科院分区：
文献类型：
--
作者：
Moalli, Federica;Doni, Andrea;Garlanda, Cecilia
Pentraxin 3 (PTX3) 是一种可溶性模式识别分子，在抗烟曲霉中发挥重要作用。本研究旨在研究 PTX3 调理活性所涉及的分子途径。 PTX3 N 端结构域负责分生孢子识别，但全长分子对于调理活性是必需的。增强中性粒细胞吞噬活性的 PTX3 依赖性途径涉及通过旁路途径激活补体； Fc gamma 受体 (Fc gamma R) IIA/CD32 识别 PTX3 致敏分生孢子和补体受体 3 (CR3) 激活； CR3和CD32定位于吞噬杯。基因靶向小鼠（ptx3、FcR 共同伽玛链、C3、C1q）验证了该通路的体内相关性。特别是，在 FcR 常见伽玛链缺陷小鼠中，外源性 PTX3 对烟曲霉的保护活性被消除。因此，PTX3 的调理和抗真菌活性处于补体、补体受体 3 和 Fc gamma R 介导的识别之间的十字路口。由于短五聚蛋白（例如 C 反应蛋白）与补体和 Fc gamma R 相互作用，因此本结果可能对先天免疫体液臂的这些成分的作用模式具有普遍意义。 （血。2010；116（24）：5170-5180）
Pentraxin 3 (PTX3) is a soluble pattern recognition molecule playing a nonredundant role in resistance against Aspergillus fumigatus. The present study was designed to investigate the molecular pathways involved in the opsonic activity of PTX3. The PTX3 N-terminal domain was responsible for conidia recognition, but the full-length molecule was necessary for opsonic activity. The PTX3-dependent pathway of enhanced neutrophil phagocytic activity involved complement activation via the alternative pathway; Fc gamma receptor (Fc gamma R) IIA/CD32 recognition of PTX3-sensitized conidia and complement receptor 3 (CR3) activation; and CR3 and CD32 localization to the phagocytic cup. Gene targeted mice (ptx3, FcR common gamma chain, C3, C1q) validated the in vivo relevance of the pathway. In particular, the protective activity of exogenous PTX3 against A fumigatus was abolished in FcR common gamma chain-deficient mice. Thus, the opsonic and antifungal activity of PTX3 is at the crossroad between complement, complement receptor 3-, and Fc gamma R-mediated recognition. Because short pentraxins (eg, C-reactive protein) interact with complement and Fc gamma R, the present results may have general significance for the mode of action of these components of the humoral arm of innate immunity. (Blood. 2010;116(24):5170-5180)