Biochemical and functional characterization of the interaction between pentraxin 3 and C1q

被引:291
作者
Nauta, AJ
Bottazzi, B
Mantovani, A
Salvatori, G
Kishore, U
Schwaeble, WJ
Gingras, AR
Tzima, S
Vivanco, F
Egido, J
Tijsma, O
Hack, EC
Daha, MR
Roos, A
机构
[1] Leiden Univ, Dept Nephrol, Med Ctr, NL-2300 RC Leiden, Netherlands
[2] Univ Milan, Mario Negri Inst Pharmacol Res, Milan, Italy
[3] Univ Milan, Inst Pathol, Milan, Italy
[4] Sigma Tau Pharmaceut Co, Pomezia, Italy
[5] Univ Oxford, John Radcliffe Hosp, MRC, Immunochem Unit, Oxford OX3 9DU, England
[6] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England
[7] Univ Leicester, Dept Microbiol & Immunol, Leicester LE1 7RH, Leics, England
[8] Univ Autonoma Madrid, Fdn Jimenez Diaz, Renal Res Lab, Madrid, Spain
[9] Univ Autonoma Madrid, Fdn Jimenez Diaz, Dept Immunol, Madrid, Spain
[10] Sanquin Res, Amsterdam, Netherlands
关键词
C1q; PTX3; complement activation;
D O I
10.1002/immu.200310022
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:465 / 473
页数:9
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