MAST-CELLS IN RUPTURE-PRONE AREAS OF HUMAN CORONARY ATHEROMAS PRODUCEAND STORE TNF-ALPHA

Background Mast cells, a cell type involved in inflammatory reactions, are present in coronary atheromas and localize to the erosion or rupt ure site of atheromas in myocardial infarction. Here we report the pre sence of TNF-alpha, a proinflammatory cytokine, in mast cells of human coronary atheromas. Methods and Results From samples of 37 coronary a rteries from subjects autopsied for medicolegal reasons, sections of t he bifurcation area of the left coronary artery were stained immunohis tochemically for mast cells and TNF-alpha. In addition, macrophages, T lymphocytes, smooth muscle cells, and endothelial cells were investig ated for their content of TNF-alpha. In normal intimas and fatty strea ks, none of the cell types studied were TNF-alpha-positive. In 14 of t he 24 atheromas found, TNF-alpha-positive cells were present. Of the t otal number of mast cells, 23% stained for TNF-alpha of the macrophage s, 1.3%; and of the smooth muscle cells, 0.4%. The majority (55%) of T NF-alpha-positive mast cells in the atheromas were located in the shou lder region and the remaining 35% in the cap and 10% in the core regio ns. Immunoelectron microscopy showed that the TNF-alpha in mast cells resided within their cytoplasmic secretory granules, demonstrating tha t these cells contain stores of TNF-alpha that will be released on deg ranulation. Conclusions This study demonstrates the presence of mast c ells with TNF-alpha-containing secretory granules, particularly in the shoulder region of human coronary atheromas. By releasing their TNF-a lpha, mast cells may play an active role in the inflammatory reactions of these rupture-prone areas of atheromas.