Nauta Alma J, Bottazzi Barbara, Mantovani Alberto, Salvatori Giovanni, Kishore Uday, Schwaeble Wilhelm J, Gingras Alexandre R, Tzima Sotiria, Vivanco Fernando, Egido Jesús, Tijsma Odette, Hack Erik C, Daha Mohamed R, Roos Anja
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Eur J Immunol. 2003 Feb;33(2):465-73. doi: 10.1002/immu.200310022.
Pentraxin 3 (PTX3) is a recently characterized member of the pentraxin family of acute-phase proteins produced during inflammation. Classical short pentraxins, C-reactive protein, and serum amyloid P component can bind to C1q and thereby activate the classical complement pathway. Since PTX3 can also bind C1q, the present study was designed to define the interaction between PTX3 and C1q and to examine the functional consequences of this interaction. A dose-dependent binding of both C1q and the C1 complex to PTX3 was observed. Experiments with recombinant globular head domains of human C1q A, B, and C chains indicated that C1q interacts with PTX3 via its globular head region. Binding of C1q to immobilized PTX3 induced activation of the classical complement pathway as assessed by C4 deposition. Furthermore, PTX3 enhanced C1q binding and complement activation on apoptotic cells. However, in the fluid-phase, pre-incubation of PTX3 with C1q resulted in inhibition of complement activation by blocking the interaction of C1q with immunoglobulins. These results indicate that PTX3 can both inhibit and activate the classical complement pathway by binding C1q, depending on the way it is presented. PTX3 may therefore be involved in the regulation of the innate immune response.
五聚体蛋白3（PTX3）是炎症期间产生的急性期蛋白五聚体家族中最近被鉴定的成员。经典的短五聚体蛋白、C反应蛋白和血清淀粉样蛋白P成分可与C1q结合，从而激活经典补体途径。由于PTX3也能结合C1q，本研究旨在确定PTX3与C1q之间的相互作用，并研究这种相互作用的功能后果。观察到C1q和C1复合物与PTX3均存在剂量依赖性结合。用人C1q A、B和C链的重组球形头部结构域进行的实验表明，C1q通过其球形头部区域与PTX3相互作用。通过C4沉积评估，C1q与固定化PTX3的结合诱导了经典补体途径的激活。此外，PTX3增强了凋亡细胞上C1q的结合和补体激活。然而，在液相中，PTX3与C1q预孵育会通过阻断C1q与免疫球蛋白的相互作用而抑制补体激活。这些结果表明，PTX3可通过结合C1q抑制和激活经典补体途径，这取决于其呈现方式。因此，PTX3可能参与先天性免疫反应的调节。
