title: Immunization with a combination of 2 peptides derived from the C5a receptor significantly reduces early atherosclerotic lesion in Ldlr(tm1Her) Apob(tm2Sgy) J mice.
abstract: OBJECTIVE
  The goal of this study was to assess whether immunization of Ldlr(tm1Her) Apob(tm2Sgy) J mice with 2 peptides located at the N-terminus of the C5a receptor (C5aR), either alone or in combination, is effective in reducing atherosclerotic lesions.
  
  
  RESULTS
  Five- to 6-week-old female Ldlr(tm1Her)Apob(tm2Sgy) J mice were immunized using a repetitive immunization multiple sites strategy with keyhole limpet hemocyanin-conjugated peptides derived from the C5aR, either alone (designated as C5aR-P1 [aa 1-21] and C5aR-P2 [aa 19-31]) or in combination (designated as C5aR-P1+C5aR-P2). Mice were fed a high-fat diet for 10 weeks. Lesions were evaluated histologically; local and systemic immune responses were analyzed by immunohistochemistry of aorta samples and cytokine measurements in plasma samples and splenocyte supernatants. Immunization of Ldlr(tm1Her)Apob(tm2Sgy) J mice with these peptides elicited high concentrations of antibodies against each peptide. Immunization with the single peptide inhibited plaque development. Combined inoculation with C5aR-P1+C5aR-P2 had an additive effect on reducing the lesion in the aorta sinus and descending aortas when compared with controls. This effect correlated with cellular infiltration and cytokine/chemokine secretion in the serum or in stimulated spleen cells as well as specific cellular immune responses when compared with controls.
  
  
  CONCLUSIONS
  Immunization of mice with C5aR-P1 and C5aR-P2, either alone or in combination, was effective in reducing early atherosclerotic lesion development. The combined peptide is more potential than either epitope alone to reduce atherosclerotic lesion formation through the induction of a specific Treg cell response as well as blockage of monocyte differentiation into macrophages.
authors: Thrombosis Research Institute, Emmanuel Kaye Bldg, Manresa Rd, London SW3 6LR, UK. xlu@tri-london.ac.uk
authors: Xinjie
authors: X
authors: Lu
authors: Min
authors: M
authors: Xia
authors: Valeria
authors: V
authors: Endresz
authors: Ildiko
authors: I
authors: Faludi
authors: Lakshmi
authors: L
authors: Mundkur
authors: Eva
authors: E
authors: Gonczol
authors: Daxin
authors: D
authors: Chen
authors: Vijay V
authors: VV
authors: Kakkar
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use*; D001011:Aorta / Q000378:metabolism / Q000473:pathology*; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D015936:Complement C5a / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D006433:Hemocyanins; D007114:Immunization / Q000379:methods; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000276:immunology / Q000627:therapeutic use; D044087:Receptor, Anaphylatoxin C5a / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000473:pathology
chemical_list: D000906:Antibodies; D016207:Cytokines; D000939:Epitopes; D010455:Peptides; D044087:Receptor, Anaphylatoxin C5a; D015936:Complement C5a; D006433:Hemocyanins