Phosphorylcholine-targeting immunization reduces atherosclerosis.
OBJECTIVE
The present study evaluated the effect of phosphorylcholine (PC) immunization on the extent of experimental atherosclerosis.


BACKGROUND
Immunization against oxidized lipoprotein (oxLDL) or Streptococcus pneumoconiae reduces atherosclerosis. Phosphorylcholine is the main epitope recognized by both antipneumococcus and anti-oxLDL antibodies. Therefore we reasoned that PC-specific antibodies might play an important role in atherogenesis.


METHODS
Apolipoprotein E knockout mice were immunized with PC every second week over 4 months. At the end of the study, serum antibodies directed to either PC or oxLDL were measured. Splenic and peritoneal B cells were analyzed by flow cytometry. Aortic root atherosclerotic lesions were quantified by morphometry and phenotyped by immunohistochemistry. Immune and control sera were also tested for their effect on foam cell formation in macrophage culture in the presence of oxLDL.


RESULTS
The PC-immunized mice showed 3-fold increase in titers of anti-PC and -oxLDL antibodies compared with control mice (p < 0.01). The PC-immunized mice also showed a significant increase in the number of splenic mature B cells. The extent of atherosclerotic aorta root lesions was reduced by >40% in the PC-immunized mice (p < 0.01). Immunohistochemistry showed reduced expression of major histocompatibility complex class II antigens (p < 0.05) and the presence of B-cell clusters in plaques of PC-immunized mice. Finally, PC-immune serum was able to reduce macrophage-derived foam cell formation in the presence of oxLDL in vitro.


CONCLUSIONS
Phosphorylcholine immunization drives a specific humoral immune response that reduces foam cell formation in vitro and is atheroprotective in vivo.
Caligiuri
Giuseppina
G
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, Paris, France. giuseppina.caligiuri@umrs681.jussieu.fr
Khallou-Laschet
Jamila
J
Vandaele
Marta
M
Gaston
Anh-Thu
AT
Delignat
Sandrine
S
Mandet
Chantal
C
Kohler
Heinz V
HV
Kaveri
Srini V
SV
Nicoletti
Antonino
A
D000818:Animals; D000906:Antibodies / Q000097:blood / Q000627:therapeutic use*; D000917:Antibody Formation / Q000502:physiology; D050197:Atherosclerosis / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D001402:B-Lymphocytes / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D007106:Immune Sera / Q000494:pharmacology; D007116:Immunization, Passive / Q000379:methods; D008077:Lipoproteins, LDL / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010767:Phosphorylcholine / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014611:Vaccination / Q000379:methods
D000906:Antibodies; D007106:Immune Sera; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D010767:Phosphorylcholine; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin