Immunization with bacillus Calmette-Guerin vaccine increases aortic atherosclerosis in the cholesterol-fed rabbit.
New Zealand White rabbits were injected subcutaneously with either a human dose of bacillus Calmette Guerin (BCG) vaccine (n = 7) or saline (n = 7). A further half dose of BCG or saline was injected after a further 4 weeks. The animals were subsequently fed a 0.25-1% cholesterol diet for 10 weeks, 8 weeks after the first injection. The rabbits were killed and perfusion fixed with 4% paraformaldehyde. The integrated plasma cholesterol levels did not differ significantly between the groups (P > 0.05). Plasma levels of anti-mycobacterial antibodies rose following BCG immunization, reaching a peak after 8 weeks (P < 0.05) compared to basal titers and the control group. BCG immunization was also associated with increased peripheral lymphocyte and monocyte activation, as evidenced by increased surface expression of IL-2 receptor (CD25) (P < 0.02) and MAC-I (CD11b) (P < 0.05), respectively. Significantly more mononuclear cells bound to the aortic endothelium of BCG immunized, cholesterol-fed rabbits (1.93+/-0.77 mononuclear cells/1000 endothelial cells) than to that of saline immunized rabbits (0.08+/-0.08 mononuclear cells/1000 endothelial cells; P < 0.01). The aortic intimal:medial ratio was greater in the BCG immunized rabbits (0.19+/-0.08) than those treated with saline (0.04+/-0.03; P < 0.05). This suggests that BCG immunization enhances peripheral leucocyte activation, aortic monocyte recruitment and atherogenesis in the cholesterol-fed rabbit.
Lamb
D J
DJ
Centre for Clinical Science and Measurement, School of Biological Sciences, University of Surrey, Guildford, UK. djll8@le.ac.uk
Eales
L J
LJ
Ferns
G A
GA
D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D001011:Aorta / Q000473:pathology; D001018:Aortic Diseases / Q000473:pathology*; D001161:Arteriosclerosis / Q000276:immunology / Q000473:pathology*; D001500:BCG Vaccine / Q000276:immunology*; D018845:CD11 Antigens / Q000032:analysis; D002448:Cell Adhesion; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D007114:Immunization; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology; D009161:Mycobacterium / Q000276:immunology; D011817:Rabbits; D015375:Receptors, Interleukin-2 / Q000032:analysis
D000907:Antibodies, Bacterial; D001500:BCG Vaccine; D018845:CD11 Antigens; D002791:Cholesterol, Dietary; D015375:Receptors, Interleukin-2; D002784:Cholesterol