title: Lactoferrin, myeloperoxidase, and ceruloplasmin: complementary gearwheels cranking physiological and pathological processes.
abstract: Copper-containing plasma protein ceruloplasmin (Cp) forms a complex with lactoferrin (Lf), an iron-binding protein, and with the heme-containing myeloperoxidase (Mpo). In case of inflammation, Lf and Mpo are secreted from neutrophil granules. Among the plasma proteins, Cp seems to be the preferential partner of Lf and Mpo. After an intraperitoneal injection of Lf to rodents, the "Cp-Lf" complex has been shown to appear in their bloodstream. Cp prevents the interaction of Lf with protoplasts of Micrococcus luteus. Upon immunoprecipitation of Cp, the blood plasma becomes depleted of Lf and in a dose-dependent manner loses the capacity to inhibit the peroxidase activity of Mpo, but not the Mpo-catalyzed oxidation of thiocyanate in the (pseudo)halogenating cycle. Antimicrobial effect against E. coli displayed by a synergistic system that includes Lf and Mpo-H2O2-chloride, but not thiocyanate, as the substrate for Mpo is abrogated when Cp is added. Hence, Cp can be regarded as an anti-inflammatory factor that restrains the halogenating cycle and redirects the synergistic system Mpo-H2O2-chloride/thiocyanate to production of hypothiocyanate, which is relatively harmless for the human organism. Structure and functions of the "2Cp-2Lf-Mpo" complex and binary complexes Cp-Lf and 2Cp-Mpo in inflammation are discussed.
authors: N-W Branch of the Russian Academy of Medical Sciences, Institute for Experimental Medicine, Pavlov Street 12, Saint Petersburg, 197376, Russia, biochemsokolov@gmail.com.
authors: Alexey V
authors: AV
authors: Sokolov
authors: Elena T
authors: ET
authors: Zakharova
authors: Elena T
authors: ET
authors: Zakahrova
authors: Valeria A
authors: VA
authors: Kostevich
authors: Valeria R
authors: VR
authors: Samygina
authors: Vadim B
authors: VB
authors: Vasilyev
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000097:blood / Q000502:physiology; D002570:Ceruloplasmin / Q000737:chemistry / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000472:pathogenicity; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007781:Lactoferrin / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016982:Micrococcus luteus / Q000187:drug effects / Q000472:pathogenicity; D008958:Models, Molecular; D009195:Peroxidase / Q000097:blood / Q000737:chemistry / Q000502:physiology*; D054730:Protein Interaction Domains and Motifs; D051381:Rats; D017208:Rats, Wistar; D013861:Thiocyanates / Q000378:metabolism / Q000494:pharmacology
chemical_list: D023181:Antimicrobial Cationic Peptides; D002712:Chlorides; D013861:Thiocyanates; D006861:Hydrogen Peroxide; D009195:Peroxidase; D002570:Ceruloplasmin; D007781:Lactoferrin; C031760:thiocyanate