EXPRESSION OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN T-LYMPHOCYTES AND MACROPHAGES OF CHOLESTEROL-FED RABBITS

While endothelial nitric oxide synthase has been reported to be expres sed in the endothelial cells of normal and atherosclerotic vessels, th ere are few reports about inducible nitric oxide synthase (INOS). We i nvestigated the expression of iNOS and its relation to inflammatory ce lls in atheroma. New Zealand White rabbits were fed 1 of 4 diets: (i) normal diet for 9 weeks; (ii) normal plus 1% cholesterol diet (atherog enic diet) for 9 weeks; (iii) atherogenic diet for 9 weeks, then norma l diet for 9 weeks; (iv) atherogenic diet for 9 weeks, then the normal diet for 36 weeks. The aortas were examined by immunohistochemical st aining for anti-iNOS antibody, as well as antibodies for macrophages, T lymphocytes, and muscle actin. No INOS was detected in normal aortas , intimal thickenings, or fatty streaks. Although iNOS was detected in necrotic cores of advanced plaque, it was not seen in smooth muscle-d erived cells or endothelial cells but was found in some macrophage-der ived cells and in T lymphocytes. In regressive atherosclerotic aortas, iNOS was detected only in necrotic cores, not in macrophage-derived c ells but in T lymphocytes. These findings suggest that T lymphocytes a nd some macrophages induce iNOS through cytokine production in atherom a. This is the first report of iNOS expression in atheromatous plaque. Copyright (C) 1997 Elsevier Science Ireland Ltd.