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.

Subject headings

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)

Keyword

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

Publication and Content Type

ref (subject category)

art (subject category)