title: Human pentraxin 3 binds to the complement regulator c4b-binding protein.
abstract: The long pentraxin 3 (PTX3) is a soluble recognition molecule with multiple functions including innate immune defense against certain microbes and the clearance of apoptotic cells. PTX3 interacts with recognition molecules of the classical and lectin complement pathways and thus initiates complement activation. In addition, binding of PTX3 to the alternative complement pathway regulator factor H was shown. Here, we show that PTX3 binds to the classical and lectin pathway regulator C4b-binding protein (C4BP). A PTX3-binding site was identified within short consensus repeats 1-3 of the C4BP α-chain. PTX3 did not interfere with the cofactor activity of C4BP in the fluid phase and C4BP maintained its complement regulatory activity when bound to PTX3 on surfaces. While C4BP and factor H did not compete for PTX3 binding, the interaction of C4BP with PTX3 was inhibited by C1q and by L-ficolin. PTX3 bound to human fibroblast- and endothelial cell-derived extracellular matrices and recruited functionally active C4BP to these surfaces. Whereas PTX3 enhanced the activation of the classical/lectin pathway and caused enhanced C3 deposition on extracellular matrix, deposition of terminal pathway components and the generation of the inflammatory mediator C5a were not increased. Furthermore, PTX3 enhanced the binding of C4BP to late apoptotic cells, which resulted in an increased rate of inactivation of cell surface bound C4b and a reduction in the deposition of C5b-9. Thus, in addition to complement activators, PTX3 interacts with complement inhibitors including C4BP. This balanced interaction on extracellular matrix and on apoptotic cells may prevent excessive local complement activation that would otherwise lead to inflammation and host tissue damage.
authors.affiliation: Junior Research Group in Cellular Immunobiology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, Jena, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Braunschweig
authors.forename: Mihály
authors.initials: M
authors.lastname: Józsi
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001665:Binding Sites; D002097:C-Reactive Protein / Q000737:chemistry / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D050716:Complement C4b-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells / Q000378:metabolism; D011485:Protein Binding; D000683:Serum Amyloid P-Component / Q000737:chemistry / Q000378:metabolism*; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D002118:Calcium; D050716:Complement C4b-Binding Protein; D000683:Serum Amyloid P-Component; D000099153:Pentraxins