MAST-CELL DISTRIBUTION, ACTIVATION, AND PHENOTYPE IN ATHEROSCLEROTIC LESIONS OF HUMAN CAROTID ARTERIES

Immunohistochemical staining for mast cell tryptase and chymase was us ed to examine the distribution, activation, and tryptase/chymase pheno type of mast cells (MCs) in 250 samples of atherosclerotic lesions (ty pe I to VI) of human carotid arteries. Dual immunolocalization and his tochemical techniques were used to identify the associations of MCs wi th macrophages, smooth muscle cells, and extracellular matrix componen ts. Whereas normal carotid arteries contained very few MCs within the intima, atherosclerotic lesions showed increased MC numbers with varia ble focal accumulations. MCs were identifiable from the earliest stage s of atherosclerosis, and especially at the shoulder regions of the fu lly formed atheroma. They were observed in close association with macr ophages (HAM56 positive) and extracellular lipid, as well as at sites of foam cell formation. MCs and diffuse tryptase staining were also ev ident within sites of new calcification and around small calcified dep osits. Extensive MC activation/degranulation, as judged by diffuse ext racellular tryptase staining, was a common feature of the advanced ath erosclerotic plaques complicated by fissure, haemorrhage, and thrombus formation. Moreover, such sites of extracellular MC tryptase were oft en associated with localized oedema and disruption of the stromal matr ix. MCs which contained both tryptase and chymase (the MCTC phenotype) represented approximately 80-95 percent of all MCs. These studies are the first to demonstrate significant numbers and focal accumulations of MCs in all developmental stages of atherosclerotic carotid arteries . Since MCs contain or express a variety of potent mediators, their re lease could profoundly influence the development and pathological comp lications of atherosclerotic plaques. (C) 1997 by John Wiley & Sons, L td.