Three pentraxins C-reactive protein, serum amyloid p component and pentraxin 3 mediate complement activation using Collectin CL-P1

• Published in: Biochimica et biophysica acta. General subjects Vol. 1861; no. 2; pp. 1 - 14
• Main Authors: Roy, Nitai, Ohtani, Katsuki, Hidaka, Yoshihiko, Amano, Yoshiro, Matsuda, Yasuyuki, Mori, Kenichiro, Hwang, Insu, Inoue, Norimitsu, Wakamiya, Nobutaka
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2017
• Subjects: Acute-Phase Reaction - metabolism; Alternative pathway; amyloid; Animals; binding proteins; blood serum; C-reactive protein; C-Reactive Protein - metabolism; Cell Line; CHO Cells; Classical pathway; Collectin; Collectins - metabolism; Complement; Complement Activation - physiology; Complement Factor H - metabolism; Complement Membrane Attack Complex - metabolism; Complement System Proteins - metabolism; Complement System Proteins - physiology; Cricetulus; enzyme-linked immunosorbent assay; HEK293 Cells; Humans; Pentraxin; Protein Binding - physiology; Serum Amyloid P-Component - metabolism; Signal Transduction - physiology; Terminal complement complex; CRP; SAP; APR; CFH; CFI; Complement; CHO; Alternative pathway; DMEM; CL-P1; FBS; Collectin; NPTX1; NPTX2; Pentraxins; Pentraxin; SR; PBS; TBS; HEK; CRD; TCC; Terminal complement complex; PTX3; NPTXR; CFB; Classical pathway; ELISA
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2016.11.023

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. 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. 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. Our current study hypothesizes that the interaction of pentraxins with CL-P1 is involved in complement activation. CL-P1 might generally inhibit PTX induced complement activation and host damage to protect self-tissues. •The interaction of CRP, SAP, and PTX3 with collectin CL-P1 activates complement mainly through the classical pathway.•Initiation of the classical pathway provokes the alternative pathway and the properdin dependent amplification pathway.•CRP and PTX3 recruit CFH while SAP recruits C4BP on CL-P1 surfaces to prevent TCC formation.•CFH, C4BP and CFI depleted serum failed to prevent TCC formation on CL-P1.