Abstract 13450: Natural Killer T Cells are Differentially Involved in the Development of Experimental Aortic Aneurysm in Mice According to Their Subtypes
Objective: The infiltration and activation of macrophages as well as lymphocytes within the vascular wall may contribute to the pathogenesis of aortic aneurysm (AA). We have demonstrated that natural killer T (NKT) cells, a unique subset of T lymphocytes which recognize glycolipid antigens and secrete a large amount of TH1/TH2 cytokines on activation, have a crucial role in the atherogenesis. Recently, CD4+ NKT cells have been shown to predominantly contribute the progression of atherosclerosis, but the other major subset, CD4-CD8- (DN) NKT cells do not. However, it remains undetermined whether NKT cells are also involved in the development of AA by the subset-dependent manner.
Methods and Results: AA was created by the infusion of angiotensin II (AngII, 1000 ng/kg/min) with osmotic minipumps for 4 weeks in male apolipoprotein E deficient (ApoE) mice or male leptin deficient ob/ob mice, which lack CD4+ NKT cells. To specifically activate NKT cells, a synthetic glycolipid OCH (0.1 μg/g body weight) was injected intraperitoneally twice a week into ApoE (ApoE-OCH; n=10) or ob/ob (ob/ob-OCH; n=15). As controls, phosphate-buffered saline (PBS) was injected in both groups of mice (ApoE-PBS; n=15 or ob/ob-PBS; n=10). Activation of NKT cells by OCH significantly increased the maximal abdominal aortic diameter (2042±327 vs. 1337±75 μm, p<0.01) in ApoE-OCH compared to ApoE-PBS without affecting the blood pressure (140±5 vs. 138±5 mmHg, p=NS). In contrast, it significantly decreased the maximal aortic diameter (1305±56 vs. 1726±117 μm, p<0.01) in ob/ob-OCH compared to ob/ob-PBS. Real-time PCR analyses demonstrated that OCH significantly enhanced the activation of macrophages, F4/80 and the major histocompatibility complex (MHC)-class II, in aortic tissues from ob/ob-OCH.
Conclusions: Activation of CD4+ NKT cells enhanced the development of AA whereas DN NKT cells ameliorated it, indicating that NKT cell subtypes are differentially involved in this disease process. Controlling the differentiation of NKT cells may be a novel therapeutic strategy for AA.
- © 2010 by American Heart Association, Inc.