title: Antibodies use heme as a cofactor to extend their pathogen elimination activity and to acquire new effector functions.
abstract: Various pathological processes are accompanied by release of high amounts of free heme into the circulation. We demonstrated by kinetic, thermodynamic, and spectroscopic analyses that antibodies have an intrinsic ability to bind heme. This binding resulted in a decrease in the conformational freedom of the antibody paratopes and in a change in the nature of the noncovalent forces responsible for the antigen binding. The antibodies use the molecular imprint of the heme molecule to interact with an enlarged panel of structurally unrelated epitopes. Upon heme binding, monoclonal as well as pooled immunoglobulin G gained an ability to interact with previously unrecognized bacterial antigens and intact bacteria. IgG-heme complexes had an enhanced ability to trigger complement-mediated bacterial killing. It was also shown that heme, bound to immunoglobulins, acted as a cofactor in redox reactions. The potentiation of the antibacterial activity of IgG after contact with heme may represent a novel and inducible innate-type defense mechanism against invading pathogens.
authors.affiliation: Department of Immunology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria; Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, UMR S 872, F-75006 Paris, France; Université Paris Descartes, UMR S 872, F-75006 Paris, France; INSERM, U872, F-75006 Paris, France. Electronic address: jdd@microbio.bas.bg.
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Dimitrov
authors.affiliation: Department of Biochemistry, Sofia University, St. Kliment Ohridsky, 1164 Sofia, Bulgaria.
authors.forename: Lubka T
authors.initials: LT
authors.lastname: Roumenina
authors.affiliation: Department of Biophysics and Radiobiology, Sofia University, St. Kliment Ohridski, 1164 Sofia, Bulgaria.
authors.forename: Virjinia R
authors.initials: VR
authors.lastname: Doltchinkova
authors.affiliation: Department of Immunology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
authors.forename: Nikolina M
authors.initials: NM
authors.lastname: Mihaylova
authors.affiliation: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, UMR S 872, F-75006 Paris, France; Université Paris Descartes, UMR S 872, F-75006 Paris, France; INSERM, U872, F-75006 Paris, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
authors.affiliation: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, UMR S 872, F-75006 Paris, France; Université Paris Descartes, UMR S 872, F-75006 Paris, France; INSERM, U872, F-75006 Paris, France.
authors.forename: Srinivas V
authors.initials: SV
authors.lastname: Kaveri
authors.affiliation: Department of Immunology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria. Electronic address: vassilev@microbio.bas.bg.
authors.forename: Tchavdar L
authors.initials: TL
authors.lastname: Vassilev
mesh_terms: D000818:Animals; D000915:Antibody Affinity; D000937:Antigen-Antibody Reactions; D001419:Bacteria / Q000187:drug effects; D001770:Blood Bactericidal Activity; D003165:Complement System Proteins / Q000276:immunology; D003486:Cyanides / Q000494:pharmacology; D006418:Heme / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007074:Immunoglobulin G / Q000276:immunology*; D007203:Indigo Carmine / Q000737:chemistry; D051379:Mice; D010084:Oxidation-Reduction; D012965:Sodium Chloride / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
chemical_list: D003486:Cyanides; D007074:Immunoglobulin G; D006418:Heme; D012965:Sodium Chloride; D003165:Complement System Proteins; D006861:Hydrogen Peroxide; D007203:Indigo Carmine