Mast cells in rupture-prone areas of human coronary atheromas produce and store TNF-alpha

Abstract

Background: Mast cells, a cell type involved in inflammatory reactions, are present in coronary atheromas and localize to the erosion or rupture site of atheromas in myocardial infarction. Here we report the presence of TNF-alpha, a proinflammatory cytokine, in mast cells of human coronary atheromas.

Methods and results: From samples of 37 coronary arteries from subjects autopsied for medicolegal reasons, sections of the bifurcation area of the left coronary artery were stained immunohistochemically for mast cells and TNF-alpha. In addition, macrophages, T lymphocytes, smooth muscle cells, and endothelial cells were investigated for their content of TNF-alpha. In normal intimas and fatty streaks, none of the cell types studied were TNF-alpha-positive. In 14 of the 24 atheromas found, TNF-alpha-positive cells were present. Of the total number of mast cells, 23% stained for TNF-alpha; of the macrophages, 1.3%; and of the smooth muscle cells, 0.4%. The majority (55%) of TNF-alpha-positive mast cells in the atheromas were located in the shoulder region and the remaining 35% in the cap and 10% in the core regions. Immunoelectron microscopy showed that the TNF-alpha in mast cells resided within their cytoplasmic secretory granules, demonstrating that these cells contain stores of TNF-alpha that will be released on degranulation.

Conclusions: This study demonstrates the presence of mast cells with TNF-alpha-containing secretory granules, particularly in the shoulder region of human coronary atheromas. By releasing their TNF-alpha, mast cells may play an active role in the inflammatory reactions of these rupture-prone areas of atheromas.