Department of Bacteriology and Immunology and Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.
HUSLAB, Helsinki University Hospital, Helsinki, Finland.
Front Immunol. 2019 Aug 2;10:1750. doi: 10.3389/fimmu.2019.01750. eCollection 2019.
The functions of pentraxins, like C-reactive protein (CRP), serum amyloid protein P (SAP) and pentraxin-3 (PTX3), are to coordinate spatially and temporally targeted clearance of injured tissue components, to protect against infections and to regulate related inflammation together with the complement system. For this, pentraxins have a dual relationship with the complement system. Initially, after a focused binding to their targets, e.g., exposed phospholipids or cholesterol in the injured tissue area, or microbial components, the pentraxins activate complement by binding its first component C1q. However, the emerging inflammation needs to be limited to the target area. Therefore, pentraxins inhibit complement at the C3b stage to prevent excessive damage. The complement inhibitory functions of pentraxins are based on their ability to interact with complement inhibitors C4bp or factor H (FH). C4bp binds to SAP, while FH binds to both CRP and PTX3. FH promotes opsonophagocytosis through inactivation of C3b to iC3b, and inhibits AP activity thus preventing formation of the C5a anaphylatoxin and the complement membrane attack complex (MAC). Monitoring CRP levels gives important clinical information about the extent of tissue damage and severity of infections. CRP is a valuable marker for distinguishing bacterial infections from viral infections. Disturbances in the functions and interactions of pentraxins and complement are also involved in a number of human diseases. This review will summarize what is currently known about the FH family proteins and pentraxins that interact with FH. Furthermore, we will discuss diseases, where interactions between these molecules may play a role.
五聚素的功能，如 C-反应蛋白（CRP）、血清淀粉样蛋白 P（SAP）和五聚素-3（PTX3），是协调受伤组织成分的时空靶向清除，以防止感染，并与补体系统一起调节相关炎症。为此，五聚素与补体系统具有双重关系。最初，在集中结合其靶标后，例如，在受伤组织区域或微生物成分中暴露的磷脂或胆固醇，五聚素通过结合其第一成分 C1q 来激活补体。然而，新出现的炎症需要局限在靶区。因此，五聚素在 C3b 阶段抑制补体以防止过度损伤。五聚素的补体抑制功能基于其与补体抑制剂 C4bp 或因子 H（FH）相互作用的能力。C4bp 结合 SAP，而 FH 结合 CRP 和 PTX3 两者。FH 通过失活 C3b 到 iC3b 促进调理吞噬作用，并抑制 AP 活性，从而防止 C5a 过敏毒素和补体膜攻击复合物（MAC）的形成。监测 CRP 水平可提供有关组织损伤程度和感染严重程度的重要临床信息。CRP 是区分细菌感染和病毒感染的有价值标志物。五聚素和补体的功能和相互作用的紊乱也与许多人类疾病有关。这篇综述将总结目前已知的与 FH 家族蛋白和与 FH 相互作用的五聚素的情况。此外，我们将讨论这些分子之间的相互作用可能起作用的疾病。
