Implication of natural killer T cells in atherosclerosis development during a LPS-induced chronic inflammation.
Atherosclerosis has many features of a chronic inflammatory disease. To evaluate the role of lipopolysaccharide (LPS), mimicking a systemic infection, we administered the endotoxin to apolipoprotein E (apoE)-deficient mice. LPS injections increase the atherosclerotic lesion size and the titer of plasma autoantibodies directed against oxidized low-density lipoprotein. We found that Th1 and Th2 T cells help the activation of B cells in the autoimmune response. The number of interleukin-4 producing natural killer T cells is highly increased in peripheral blood, liver, spleen and thymus cells, as well as in the atherosclerotic plaque of the LPS-treated mice. Finally, an important adventitial infiltrate of activated lymphocytes, sign of an advanced atherosclerosis, is observed only in the LPS-treated mice. Our results demonstrate that LPS administration aggravates atherosclerosis in apoE-deficient mice. LPS-injected apoE-deficient mice appear to be an excellent animal model to analyze the implementation of new therapeutic approaches in the treatment of atherosclerosis by manipulating immunological effectors.
Ostos
Maria A
MA
Unité d'Expression des Gènes Eucaryotes, Institut Pasteur, Paris, France.
Recalde
Delia
D
Zakin
Mario M
MM
Scott-Algara
Daniel
D
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D005434:Flow Cytometry; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000097:blood; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL / Q000276:immunology; D008099:Liver / Q000473:pathology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D013950:Thymus Gland / Q000473:pathology
D001057:Apolipoproteins E; D001323:Autoantibodies; D016207:Cytokines; D008055:Lipids; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D015847:Interleukin-4