The IgM response to modified LDL in experimental atherosclerosis: hypochlorite-modified LDL IgM antibodies versus classical natural T15 IgM antibodies.
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.
van Leeuwen
Marcella
M
Internal Medicine, Clinical and Experimental Immunology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
Damoiseaux
Jan
J
Duijvestijn
Adriaan
A
Heeringa
Peter
P
Gijbels
Marion
M
de Winther
Menno
M
Tervaert
Jan Willem Cohen
JW
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
D004041:Dietary Fats; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D006997:Hypochlorous Acid; D002784:Cholesterol