Three pentraxins C-reactive protein, serum amyloid p component and pentraxin 3 mediate complement activation using Collectin CL-P1
| Autor: | Kenichiro Mori, Norimitsu Inoue, Yoshiro Amano, Yasuyuki Matsuda, Insu Hwang, Nobutaka Wakamiya, Katsuki Ohtani, Nitai Roy, Yoshihiko Hidaka |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Complement receptor 1 Biophysics Complement Complement factor I CHO Cells Complement Membrane Attack Complex Biochemistry Cell Line 03 medical and health sciences Classical complement pathway 0302 clinical medicine Cricetulus Alternative pathway Animals Humans Acute-Phase Reaction Molecular Biology Complement Activation biology Pentraxins Chemistry Complement System Proteins Pentraxin Molecular biology Collectins Complement system Collectin Serum Amyloid P-Component 030104 developmental biology C-Reactive Protein HEK293 Cells Terminal complement complex Factor H Complement Factor H Classical pathway Alternative complement pathway biology.protein biology.gene CFHR5 030215 immunology Protein Binding Signal Transduction |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - General Subjects. 1861(2):1-14 |
| Popis: | Background Pentraxins (PTXs) are a superfamily of multifunctional conserved proteins involved in acute-phase responses. Recently, we have shown that collectin placenta 1 (CL-P1) and C-reactive protein (CRP) mediated complement activation and failed to form terminal complement complex (TCC) in normal serum conditions because of complement factor H inhibition. Methods We used CL-P1 expressing CHO/ldlA7 cells to study the interaction with PTXs. Soluble type CL-P1 was used in an ELISA assay for the binding, C3 and TCC deposition experiments. Furthermore, we used our previously established CL-P1 expressing HEK293 cells for the C3 fragment and TCC deposition assay. Results We demonstrated that CL-P1 also bound serum amyloid p component (SAP) and pentraxin 3 (PTX3) to activate the classical pathway and the alternative pathway using factor B. CRP and PTX3 further amplified complement deposition by properdin. We found that CRP and PTX3 recruit CFH, whereas SAP recruits C4 binding protein on CL-P1 expressing cell surfaces to prevent the formation of TCC in normal serum conditions. In addition, depletion of CFH, C4BP and complement factor I (CFI) failed to prevent TCC formation both in ELISA and cell experiments. Furthermore, soluble complement receptor 1, an inhibitor of all complement pathways prevents PTX induced TCC formation. Conclusion Our current study hypothesizes that the interaction of pentraxins with CL-P1 is involved in complement activation. General significance CL-P1 might generally inhibit PTX induced complement activation and host damage to protect self-tissues. |
| Databáze: | OpenAIRE |
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