title: The IgM response to modified LDL in experimental atherosclerosis: hypochlorite-modified LDL IgM antibodies versus classical natural T15 IgM antibodies.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Internal Medicine, Clinical and Experimental Immunology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Marcella
authors.initials: M
authors.lastname: van Leeuwen
authors.forename: Jan
authors.initials: J
authors.lastname: Damoiseaux
authors.forename: Adriaan
authors.initials: A
authors.lastname: Duijvestijn
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
authors.forename: Marion
authors.initials: M
authors.lastname: Gijbels
authors.forename: Menno
authors.initials: M
authors.lastname: de Winther
authors.forename: Jan Willem Cohen
authors.initials: JW
authors.lastname: Tervaert
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood* / Q000209:etiology; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats / Q000008:administration & dosage / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006997:Hypochlorous Acid / Q000737:chemistry / Q000378:metabolism*; D007075:Immunoglobulin M / Q000097:blood* / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D006997:Hypochlorous Acid; D002784:Cholesterol