Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans.

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of oxidized lipoproteins and apoptotic cells. Adaptive immune responses to various oxidation-specific epitopes play an important role in atherogenesis. However, accumulating evidence suggests that these epitopes are also recognized by innate receptors, such as scavenger receptors on macrophages, and plasma proteins, such as C-reactive protein (CRP). Here, we provide multiple lines of evidence that oxidation-specific epitopes constitute a dominant, previously unrecognized target of natural Abs (NAbs) in both mice and humans. Using reconstituted mice expressing solely IgM NAbs, we have shown that approximately 30% of all NAbs bound to model oxidation-specific epitopes, as well as to atherosclerotic lesions and apoptotic cells. Because oxidative processes are ubiquitous, we hypothesized that these epitopes exert selective pressure to expand NAbs, which in turn play an important role in mediating homeostatic functions consequent to inflammation and cell death, as demonstrated by their ability to facilitate apoptotic cell clearance. These findings provide novel insights into the functions of NAbs in mediating host homeostasis and into their roles in health and diseases, such as chronic inflammatory diseases and atherosclerosis.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Mikrobiologi inom det medicinska området hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Microbiology in the medical area hsv//eng
Adoptive Transfer
Animals
Antibody Affinity
immunology
Antibody Formation
immunology
Antibody Specificity
immunology
Apoptosis
immunology
Atherosclerosis
immunology
pathology
B-Lymphocyte Subsets
immunology
transplantation
Epitopes
immunology
Female
Fetal Blood
immunology
Germ-Free Life
immunology
Homeodomain Proteins
genetics
Immunity
Innate
immunology
Immunoglobulin M
blood
immunology
Lipoproteins
LDL
immunology
Macrophages
Peritoneal
immunology
Male
Malondialdehyde
analogs & derivatives
immunology
Mice
Mice
Inbred C57BL
Mice
Knockout
Oxidation-Reduction
Phagocytosis
immunology
Phosphorylcholine
analogs & derivatives
immunology
Receptors
LDL
genetics
Serum Albumin
Bovine
immunology

Fogelstrand, Linda,1974Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory(Swepub:gu)xsvlin (author)
Hartvigsen, Karsten (author)
Hansen, Lotte F (author)
Woelkers, Douglas (author)
Shaw, Peter X (author)
Choi, Jeomil (author)
Perkmann, Thomas (author)
Bäckhed, Fredrik,1973Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory(Swepub:gu)xbafre (author)
Miller, Yury I (author)
Hörkkö, Sohvi (author)
Corr, Maripat (author)
Witztum, Joseph L (author)
Binder, Christoph J (author)
Göteborgs universitetWallenberglaboratoriet (creator_code:org_t)

By the author/editor: Chou, Meng-Yun; Fogelstrand, Lin ...; Hartvigsen, Kars ...; Hansen, Lotte F; Woelkers, Dougla ...; Shaw, Peter X; show more...; Choi, Jeomil; Perkmann, Thomas; Bäckhed, Fredrik ...; Miller, Yury I; Hörkkö, Sohvi; Corr, Maripat; Witztum, Joseph ...; Binder, Christop ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Microbiology in ...

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