ABSTRACT
In order to determine the effect of antibodies against electronegative low-density lipoprotein LDL(-) on atherogenesis, five groups of LDL low receptor-deficient (LDLr-/-) mice (6 per group) were immunized with the following antibodies (100 µg each): mouse anti-LDL(-) monoclonal IgG2b, rabbit anti-LDL(-) polyclonal IgG or its Fab fragments and mouse irrelevant monoclonal IgG and non-immunized controls. Antibodies were administered intravenously one week before starting the hypercholesterolemic diet (1.25 percent cholesterol) and then every week for 21 days. The passive immunization with anti-LDL(-) monoclonal IgG2b, polyclonal antibody and its derived Fab significantly reduced the cross-sectional area of atherosclerotic lesions at the aortic root of LDLr-/- mice (28.8 ± 9.7, 67.3 ± 17.02, 56.9 ± 8.02 µm² (mean ± SD), respectively) compared to control (124.9 ± 13.2 µm²). Vascular cell adhesion molecule-1 protein expression, quantified by the KS300 image-analyzing software, on endothelium and the number of macrophages in the intima was also decreased in aortas of mice treated with anti-LDL(-) monoclonal antibody (3.5 ± 0.70 per field x 10) compared to controls (21.5 ± 3.5 per field x 10). Furthermore, immunization with the monoclonal antibody decreased the concentration of LDL(-) in blood plasma (immunized: 1.0 ± 1.4; control: 20.5 ± 3.5 RLU), the amount of cholesterol oxides in plasma (immunized: 4.7 ± 2.7; control: 15.0 ± 2.0 pg COx/mg cholesterol) and liver (immunized: 2.3 ± 1.5; control: 30.0 ± 26.0 pg COx/mg cholesterol), and the hepatic content of lipid hydroperoxides (immunized: 0.30 ± 0.020; control: 0.38 ± 0.15 ng/mg protein). In conclusion, antibodies against electronegative LDL administered intravenously may play a protective role in atherosclerosis.
Subject(s)
Animals , Female , Mice , Rabbits , Antibodies, Monoclonal/administration & dosage , Atherosclerosis/therapy , Immunization, Passive/methods , Immunoglobulin G/administration & dosage , Lipoproteins, LDL/administration & dosage , Receptors, LDL/immunology , Antibodies, Monoclonal/immunology , Atherosclerosis/immunology , Atherosclerosis/metabolism , Immunohistochemistry , Immunoglobulin Fab Fragments/administration & dosage , Immunoglobulin Fab Fragments/immunology , Immunoglobulin G/immunology , Lipid Peroxidation/immunology , Lipoproteins, LDL/immunology , Receptors, LDL/metabolism , Vascular Cell Adhesion Molecule-1/immunologySubject(s)
Host-Parasite Interactions , Macrophages/parasitology , Trypanosoma cruzi/physiology , Adjuvants, Immunologic/pharmacology , Immunoglobulin Fab Fragments/immunology , Macrophages/immunology , Macrophages/ultrastructure , Receptors, Complement , Receptors, Immunologic , Trypanosoma cruzi/immunology , Trypanosoma cruzi/ultrastructureABSTRACT
The finding that Fab fragments of the anti-E1 Tor haemagglutinin were able to afford protection in vivo (low but significant), as well as a significant reduction in Vibrio cholerae adherence to isolated intestinal epithelial cells in-vitro, implicate that masking of these cell-bound haemagglutinin sites per se, would be sufficient to confer protection in E1 Tor cholera infection. Subsequently, the related working hypothesis that the E1 Tor cell-bound haemagglutinin is playing an adhesive role is validated. In natural immunity, it could be envisaged that antiserum to this cell-bound haemagglutinin of V. cholerae E1 Tor would be highly protective due to the synergistic effects of the dual protective mechanisms in operation at the intestinal sites viz. a masking and agglutinating phenomenon.