The IgM response to modified LDL in experimental atherosclerosis: hypochlorite-modified LDL IgM antibodies versus classical natural T15 IgM antibodies

Ann N Y Acad Sci. 2009 Sep;1173:274-9. doi: 10.1111/j.1749-6632.2009.04657.x.

Abstract

Introduction: It is hypothesized that IgM antibodies to oxidized LDL are anti-atherogenic. Myeloperoxidase from plaque-infiltrating neutrophils catalyzes the production of hypochlorite (HOCl), which oxidizes LDL. Here we study the IgM response to HOCl-modified LDL in comparison to titers of T15 clonotypic natural antibodies.

Methods: Plasma of LDLR(-/-) mice fed a normal chow or high-fat diet was obtained after 6 and 16 weeks. The IgM responses to HOCl-modified LDL and T15 clonotypic natural IgM antibodies were measured by ELISA.

Results: The IgM levels in response to HOCl-modified LDL increased dramatically in the atherosclerotic group after introduction of the high-fat diet, but not in mice on normal chow. The natural IgM T15 clonotypic antibody titers revealed a more moderate increase during atherogenesis.

Conclusion: Our results show that during atherogenesis there is a strong induction of IgM antibodies to HOCl-modified LDL particles. Whether these induced IgM antibodies are pro- or anti-atherogenic remains to be established.

MeSH terms

  • Animals
  • Atherosclerosis / blood*
  • Atherosclerosis / etiology
  • Cholesterol / blood
  • Dietary Fats / administration & dosage
  • Dietary Fats / toxicity
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Hypochlorous Acid / chemistry
  • Hypochlorous Acid / metabolism*
  • Immunoglobulin M / blood*
  • Immunoglobulin M / chemistry
  • Lipoproteins, LDL / blood*
  • Lipoproteins, LDL / chemistry
  • Lipoproteins, LDL / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oxidation-Reduction
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism

Substances

  • Dietary Fats
  • Immunoglobulin M
  • Lipoproteins, LDL
  • Receptors, LDL
  • Hypochlorous Acid
  • Cholesterol