Human heart mast cell and its role in cardiovascular disease

Human mast cells and basophils, described by Paul Ehrlich in 1879, are unique inflammatory cells in being the only cells to express the tetrameric (αβγ₂)structure of the high affinity receptor for IgE (FcåRI) and to synthesize histamine. The human mast cell is a tissue-based immune cell of bone marrow origin. Mast cells produce a vast array of mediators (preformed and lipid mediators, cytokines, and chemokines) and this variety accounts for the unique features of the mast cells in the immune system. Mast cells are present in human heart and in the inflammatory infiltrate in human atherosclerotic lesions. The immunologic and ultrastructural characterization of human heart mast cells in situ and in vitro has provided new information. Mast cells are present in normal, and even more abundant, in diseased human heart tissue. Within heart tissue, mast cells lie between myocytes, in close contact with blood vessels. These cells are also found in the coronary adventitia and in the shoulder region of coronary atheromas and in abdominal aortic aneurisms. The density of human heart mast cells is higher in some patients with idiopathic and ischemic cardiomyopathy than in accident victims without cardiovascular diseases. Importantly, in some of these conditions there is in situ evidence of mast cell activation. The immunologic activation of isolated heart mast cells in vitro leads to the release of preformed (histamine, tryptase, chymase and carboxypeptidase), de novo synthesized mediators (prostaglandin D2 and cysteinyl leukotriene C₄) and cytokines, which may have profound effects in several cardiovascular disorders. These results support the hypothesis that mast cells and their mediators can play roles in the early and late stages of atherogenesis, during myocardial ischemia, and in dilated cardiomyopathies.