Complement-regulator factor H and related proteins in otitis media with effusion
Complement-regulator factor H and related proteins in otitis media with effusion
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DOI：
10.1006/clim.2001.5043
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发表时间：
2001-07-01
影响因子：
8.6
通讯作者：
Meri, S
中科院分区：
文献类型：
--
作者：
Närkiö-Mäkelä, M;Hellwage, J;Meri, S
渗出性中耳炎(OME)是儿童的常见病。它的特点是慢性炎症，补体(C)系统的促炎活性是其潜在因素之一。C系统在中耳积液中被强烈激活，但其原因尚不清楚。在这里，我们通过使用补体BB片段的酶联免疫吸附试验证明，MEE标本强烈激活了正常人血清(NHS)中的替代C途径(AP)。NHS还发现部分MEES对兔红细胞有促进裂解作用。这些发现提示MEE患者AP的液相调节功能紊乱。AP的主要调节因子H因子(FH)及其结构相关蛋白(FHL-1、FHR-1、-2、-3和-4)存在于OME患者的MEE液中。相对于血清，蛋鸡的FHR蛋白更为丰富。此外，我们还在MEE中检测到了最近发现的65 kDa FH相关蛋白FHR-5。FHR蛋白与FH在C3b的C3d区有相同的结合部位。因此，它们可能与FH在结合C3b方面竞争，并干扰FH的调节活性。因此，MEE中AP控制的紊乱可能导致OME中持续的C过度激活和炎症。(C)2001年学术出版社。
Otitis media with effusion (OME) is a common disease in childhood. It is characterized by chronic inflammation in which the proinflammatory activity of the complement (C) system is one of the underlying factors. The C system becomes strongly activated in the middle ear effusion (MEE) fluid, but the reasons for this are not known. Here we demonstrate by using complement Bb fragment ELISA that MEE specimens strongly activate the alternative C pathway (AP) in normal human serum (NHS). Some of the MEEs were also found to promote lysis of rabbit erythrocytes by NHS. These findings indicated a disturbance in the fluid-phase regulation of the AP in MEE. The main regulator of the AP, factor H (FH), and proteins structurally related to it (FHL-1, FHR-1, -2, -3, and -4) were present in the MEE fluids of OME patients. Relative to serum, the FHR proteins were more abundant in the MEEs. In addition, we detected the recently discovered 65-kDa FH-related protein FHR-5 in the MEE. The FHR proteins share binding sites with FH in the C3d region of C3b. Thus they may compete with FH in binding to C3b and interfere with the regulatory activity of FH. Consequently, a disturbance in AP control in the MEE may lead to an ongoing excessive C activation and inflammation in OME. (C) 2001 Academic Press.