title: Three pentraxins C-reactive protein, serum amyloid p component and pentraxin 3 mediate complement activation using Collectin CL-P1.
abstract: 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.
authors.affiliation: Department of Microbiology & Immunochemistry, Asahikawa Medical University, Asahikawa 078-8510, Japan.
authors.forename: Nitai
authors.initials: N
authors.lastname: Roy
authors.affiliation: Department of Microbiology & Immunochemistry, Asahikawa Medical University, Asahikawa 078-8510, Japan.
authors.forename: Katsuki
authors.initials: K
authors.lastname: Ohtani
authors.affiliation: Department of Pediatrics, School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hidaka
authors.affiliation: Department of Pediatrics, Nagano Red Cross Hospital, 5-22-1 Wakasato, Nagano 380-8582, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Amano
authors.affiliation: Department of Microbiology & Immunochemistry, Asahikawa Medical University, Asahikawa 078-8510, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Matsuda
authors.affiliation: Department of Microbiology & Immunochemistry, Asahikawa Medical University, Asahikawa 078-8510, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Mori
authors.affiliation: Department of Microbiology & Immunochemistry, Asahikawa Medical University, Asahikawa 078-8510, Japan.
authors.forename: Insu
authors.initials: I
authors.lastname: Hwang
authors.affiliation: Department of Tumor Immunology, Research Institute, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Inoue
authors.affiliation: Department of Microbiology & Immunochemistry, Asahikawa Medical University, Asahikawa 078-8510, Japan. Electronic address: wakamiya@asahikawa-med.ac.jp.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Wakamiya
mesh_terms: D000210:Acute-Phase Reaction / Q000378:metabolism; D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism*; D016466:CHO Cells; D002460:Cell Line; D037222:Collectins / Q000378:metabolism*; D003167:Complement Activation / Q000502:physiology*; D017242:Complement Factor H / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism / Q000502:physiology; D003412:Cricetulus; D057809:HEK293 Cells; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D037222:Collectins; D017242:Complement Factor H; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins; D000683:Serum Amyloid P-Component; D000099153:Pentraxins
keywords: Alternative pathway; Classical pathway; Collectin; Complement; Pentraxin; Terminal complement complex