Dose-Dependent Induction of an Idiotypic Cascade by Anti-Glycosaminoglycan Monoclonal Antibody in apoE−/− Mice: Association with Atheroprotection
| Autor: | Sylvie Marleau, Roger Sarduy, Ana María Vázquez, Yosdel Soto, Victor Brito, Adriana del Carmen Gutiérrez Castillo, Tania Griñán |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Apolipoprotein B medicine.drug_class Immunology Dose dependence 030204 cardiovascular system & hematology Monoclonal antibody Glycosaminoglycan 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Sulfation Internal medicine Internal Medicine medicine Immunology and Allergy antibodies idiotypic cascade Foam cell biology Apoe mice Chemistry atheroprotection General Medicine 030104 developmental biology Endocrinology Immunization glycosaminoglycans monoclonal antibody Low-density lipoprotein biology.protein Antibody atherosclerosis Cardiology and Cardiovascular Medicine |
| Zdroj: | Frontiers in Immunology. 8 |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2017.00232 |
| Popis: | Atherosclerosis, the underlying pathology of most cardiovascular diseases, is triggered by the retention of apolipoprotein B (apoB)-containing lipoproteins in the arterial wall, through electrostatic interactions with glycosaminoglycan (GAG) side chains of proteoglycans. Previously, we reported the antiatherogenic properties of the chimeric monoclonal antibody (mAb) chP3R99-LALA, which binds sulfated GAGs, inhibits low density lipoprotein (LDL)-chondroitin sulfate (CS) association and abrogates LDL oxidation and foam cell formation. In preventive and therapeutic settings, apoE-deficient (apoE-/-) mice immunized with 50 µg of this mAb showed reduced atherosclerotic lesions, related with the induction of autologous anti-GAG antibodies. Knowing that age and sex are major non-modifiable risk factors in the development of atherosclerosis, the present study aimed to assess the influence of these variables on the capacity of chP3R99-LALA mAb to generate an anti-CS antibody response. Also, we aimed at defining the impact of the dose of chP3R99-LALA on the anti-CS antibody induction and the atheroprotective effect of this mAb in apoE-/- mice. Neither age nor sex had an impact in the IgG anti-chondroitin sulfate (CS) antibody response induced by s.c. immunization with this mAb. Moreover, chP3R99-LALA mAb reduced atherosclerotic lesions to a similar extent in both young male and female apoE-/- mice fed a hypercholesterolemic diet and in middle-aged female apoE-/- mice with spontaneous lesions. On the other hand, increasing the dose of chP3R99-LALA (200 µg vs 50 µg) elicited an anti-idiotype antibody cascade characterized by higher levels of anti-idiotype (Ab2), anti-anti-idiotype (Ab3) and anti-CS antibody responses. Moreover, this dose increment resulted in a striking reduction of aortic atherosclerotic lesions in immunized mice. |
| Databáze: | OpenAIRE |
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