Biochemical and functional characterization of the interaction between pentraxin 3 and C1q.
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.
Nauta
Alma J
AJ
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. nauta@lumc.nl
Bottazzi
Barbara
B
Mantovani
Alberto
A
Salvatori
Giovanni
G
Kishore
Uday
U
Schwaeble
Wilhelm J
WJ
Gingras
Alexandre R
AR
Tzima
Sotiria
S
Vivanco
Fernando
F
Egido
Jesús
J
Tijsma
Odette
O
Hack
Erik C
EC
Daha
Mohamed R
MR
Roos
Anja
A
D017209:Apoptosis; D002097:C-Reactive Protein / Q000737:chemistry* / Q000378:metabolism; D015922:Complement C1q / Q000737:chemistry* / Q000378:metabolism; D003171:Complement Pathway, Classical / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000737:chemistry* / Q000378:metabolism; D000099153:Pentraxins
D002097:C-Reactive Protein; D015922:Complement C1q; D011993:Recombinant Fusion Proteins; D000683:Serum Amyloid P-Component; D000099153:Pentraxins