Ferrous ions and reactive oxygen species increase antigen-binding and anti-inflammatory activities of immunoglobulin G.
Polyspecific antibodies represent a first line of defense against infection and regulate inflammation, properties hypothesized to rely on their ability to interact with multiple antigens. We demonstrated that IgG exposure to pro-oxidative ferrous ions or to reactive oxygen species enhances paratope flexibility and hydrophobicity, leading to expansion of the spectrum of recognized antigens, regulation of cell proliferation, and protection in experimental sepsis. We propose that ferrous ions, released from transferrin and ferritin at sites of inflammation, synergize with reactive oxygen species to modify the immunoglobulins present in the surrounding microenvironment, thus quenching pro-inflammatory signals, while facilitating neutralization of pathogens.
Dimitrov
Jordan D
JD
Department of Immunology, Stefan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Ivanovska
Nina D
ND
Lacroix-Desmazes
Sébastien
S
Doltchinkova
Virjinia R
VR
Kaveri
Srinivas V
SV
Vassilev
Tchavdar L
TL
D000818:Animals; D000918:Antibody Specificity / Q000502:physiology; D000937:Antigen-Antibody Reactions / Q000502:physiology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007074:Immunoglobulin G / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007501:Iron / Q000276:immunology* / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D011487:Protein Conformation; D017382:Reactive Oxygen Species / Q000276:immunology* / Q000378:metabolism; D013816:Thermodynamics
D007074:Immunoglobulin G; D017382:Reactive Oxygen Species; D007501:Iron