Inflammatory Fats

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Science  13 Feb 2004:
Vol. 303, Issue 5660, pp. 927
DOI: 10.1126/science.303.5660.927c

Atherosclerosis is a complex disease with multiple associated risk factors. Increasingly apparent among these are the inflammatory events that arise from the interplay between plasma lipoproteins, the arterial wall, and the immune system. T cells and macrophages are thought to dominate in these inflammatory events, although other immune cells may also play a pro-inflammatory role.

To test whether natural killer T (NKT) cells might participate in atherogenesis, Turin et al. employed mice with a deficiency in apolipoprotein E (ApoE), a major plasma constituent involved in cholesterol transport. In these animals, an excess of cholesterol leads to the spontaneous development of atherosclerosis. Injection of ApoE-deficient mice with an artificial glycolipid known to activate NKT cells increased the severity of atherosclerotic lesions and amplified inflammatory cytokine production. This aggravation of disease required expression of CD1d, the protein responsible for presenting lipid antigens to NKT cells. Similarly, the spontaneous development of atherosclerosis in ApoE-deficient mice was less severe in the absence of CD1d. Thus, lipids that accumulate at atherogenic sites may contribute to inflammation through direct immune cell activation and could represent targets for therapeutic intervention in atherosclerosis. — SJS

J. Exp. Med. 199, 417 (2004).

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