MAST-CELLS OF 2 TYPES DIFFERING IN NEUTRAL PROTEASE COMPOSITION IN THE HUMAN AORTIC INTIMA - DEMONSTRATION OF TRYPTASE-CONTAINING AND TRYPTASE CHYMASE-CONTAINING MAST-CELLS IN NORMAL INTIMAS, FATTY STREAKS ANDTHE SHOULDER REGION OF ATHEROMAS/

Biochemical studies in vitro have demonstrated that stimulated mast ce lls induce macrophage foam cell formation through the synergistic acti on of mast cell granule neutral proteases and proteoglycans. To determ ine the presence and number of mast cells in human arterial intima, th e site of atherogenesis, specimens of normal and atherosclerotic human aortic intima from 35 autopsies of persons ranging from 13 to 67 year s old were stained with monoclonal antibodies against the two major pr oteases of mast cells, tryptase and chymase. All mast cells present we re found to contain tryptase, and an average of 40% contained chymase as well. In sections of normal intimas, fatty streaks, and atheromas, the mast cells had average densities of 15/mm(2), 15/mm(2), and 3/mm(2 ), respectively. In contrast to the normal intimas and fatty streaks, however, the atheromas had mast cells distributed unevenly in a typica l pattern: 8/mm(2) in the shoulder region, 1/mm(2) in the fibrous cap, and none in the core region. In normal intimas, fatty streaks, and th e shoulder region of atheromas, the mast cells amounted to 3% of all n ucleated cells. The ratios of mast cells to T lymphocytes and to macro phages, respectively, were 2:1 and 1:4 in normal intimas, 1:3 and 1:10 in fatty streaks, and 1:5 and 1:20 in the shoulder region of atheroma s. Thus, among the blood-borne cells in the human aortic intima, mast cells compose a significant cell population, and in terms of their pro tease content, these intimal mast cells are heterogeneous. The presenc e of mast cells in fatty streaks (the site of foam cell formation) and in the shoulder region, ie, the growing edge, of atheromas supports t he hypothesis that mast cells play a role in both the early and late s tages of atherogenesis.