Serum amyloid P component binds to histones and activates the classical complement pathway.
Two members of the pentraxin family of proteins, C-reactive protein (CRP) and serum amyloid P component (SAP), bind to chromatin and may be involved in the solubilization and clearance of nuclear material. Previous studies demonstrated that CRP binding to chromatin is mediated by histones. SAP differs from CRP in being able to bind to DNA, but SAP binding to histones has not been reported. CRP is an activator of the classical C pathway, and C-dependent cleavage of chromatin in the presence of CRP and serum has been shown. Oligomers of SAP have recently been found to bind to C1q and consume total C and C4, indicating that SAP can activate C as well. The present study examined CRP and SAP binding to histones H1 and H2A and C activation after binding. SAP binding to histones H1 and H2A was observed as well as SAP binding to chromatin. In contrast to CRP, SAP binding to chromatin did not require H1. SAP partially inhibited CRP binding to chromatin and to H1. However, neither pentraxin inhibited binding of the other to H2A. Binding of either CRP or SAP to H2A activated C in SAP-depleted serum leading to the deposition of C4 and C3. C activation required C1q and produced C4d indicating that it occurred through the classical pathway. These findings demonstrate that CRP and SAP share histone as well as chromatin binding, and that both pentraxins can activate the classical C pathway after ligand binding.
Hicks
P S
PS
Department of Microbiology, University of New Mexico School of Medicine, Albuquerque 87131.
Saunero-Nava
L
L
Du Clos
T W
TW
Mold
C
C
D000818:Animals; D001667:Binding, Competitive; D002097:C-Reactive Protein / Q000378:metabolism*; D015922:Complement C1q / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D003171:Complement Pathway, Classical; D006657:Histones / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D011485:Protein Binding; D000683:Serum Amyloid P-Component / Q000276:immunology / Q000378:metabolism*
D003181:Complement C4; D006657:Histones; D000683:Serum Amyloid P-Component; D015922:Complement C1q; D002097:C-Reactive Protein