Cardiac mast cell

In this article we will describe the possible roles of cardiac mast cells and their mediators during anaphylactic reactions in man and will briefly review the cardiovascular effects of mast cell-derived mediators in vivo. 

We have identified mast cells around blood vessels and between myocardial fibers in all sections of human hearts [16,17]. These cells are also seen in normal and atherosclerotic human arterial intima [ 18-21 ]. In situ electron microscopy of cardiac mast cells revealed a small percentage (about 5%) of activated, i.e. partially degranulated mast cells [16,22]. This is clinically relevant because it implies that immunologic and non-immunologic stimuli can activate HHMC to release vasoactive and proinflammatory mediators [23]. 

Mast cells are present in the normal human heart and even more abundant in diseased hearts [ 16-18,25,47]. Within heart tissue, mast cells he between myocytes and are in close contact with blood vessels. They are also found in the coronary adventitia and in the shoulder regions of coronary atheroma [20, 21], The density of cardiac mast cells is higher in patients with dilated and ischemic cardiomyopathy than in accident victims without cardiovascular diseases [25], Importantly, in some of these conditions there is in situ evidence of mast cell activation [16,34],... 

Marone G. de Crescenzo G. Florio G, Granata F, Dente V. Genovese A Immunological modulation of human cardiac mast cells. Neurochem Res 1999 24 1195. 

Urata H, Kinoshita A, Misono KS, Bumpus FM. Husain A Identification of a highly specific chy-mase as the major angiotensin Il-forming enzyme in the human heart. J Biol Chem 1990 265 22348. Silver RB, Reid AC, Mackins CJ, Askwith T, Schaefer U, Herzlinger D, Levi R Mast cells a unique source of renin. Proc Natl Acad Sci USA 2004 101 13607. Mackins CJ, Kano S, Sevedi N, Schafer U, Reid AC, Machida T, Silver RB, Levi R Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion. J Clin Invest 2006 116 1063. 

Rakusan, K. and Campbell, S.E. (1991). Spatial relationship between cardiac mast cells and coronary capillaries in neonatal rats with cardiomegaly. Can. J. Physiol. Pharmacol. 69, 1750-1753. 

We evaluated the effects of increasing concentrations of protein Fv obtained from patients suffering from HCV on the activation of human cardiac mast cells [58], Low concentrations of protein Fv concentration-dependently... 

Fig. 4. Effects of increasing concentrations of proteins Fv and anti-IgE on histamine release from human cardiac mast cells from seven donors. Protein Fv from donors FAR and TER was absorbed or nonabsorbed with protein A-Sepharose coated with polyclonal IgG. Cells were challenged with protein Fv or anti-IgE for 30 min at 37°C. Values are expressed as mean SEM. Error bars are not shown when graphically too small. (Reproduced with permission from Genovese et al. [58].)... 

Secretory granules of cardiac mast cells contain tryptase as well as histamine [31], We found a significant correlation between the maximum histamine and tryptase release indicating that protein Fv releases tryptase in parallel with... 

To assess the mechanism by which protein Fv activates cardiac mast cells, the protein was preincubated with human monoclonal IgM of different VH families [63], Preincubation of mast cells with preparations of monoclonal IgM that possess a VH3 domain concentration-dependently inhibited the releasing activity of protein Fv. By contrast, preincubation with a monoclonal IgM Vh6+ had no such effect. These results suggest that binding to the VH3 domain inhibits the binding of protein Fv to IgE bound to FceRI on cardiac mast cells. 

Also of interest is the observation that protein Fv is a potent inducer of mediator release from mast cells isolated from human heart tissue [58,63]. This represents the first evidence that a human protein induced by viral infections can act as an endogenous immunoglobulin superantigen causing the release of vasoactive and immunoregulatory mediators from cardiac mast cells. 

Although there are no data about the serum concentrations of protein Fv in different pathophysiological conditions, it is not inconceivable that this protein synthesized by the liver in patients with acute and chronic viral hepatitis infections can contribute, through the release of mediators from cardiac mast cells, to some of the cardiovascular manifestations observed in some of these patients [45—48]. 

HCV has been associated with many extrahepatic manifestations [35, 36, 67], including myocarditis and cardiomyopathy [68, 69]. Histological and functional observations have led to the hypothesis that mast cells play an important role in many fibrotic reactions [70-72], Potential mast cell-derived mediators of the fibrotic response include histamine, tryptase and TGF-fl, which stimulate fibroblast proliferation and collagen synthesis [73-75]. By producing these factors, chronic activation of cardiac mast cells by protein Fv may contribute to the heart fibrosis found in some patients with HCV infection [68, 69]. 

Bankl HC, Radaszkiewicz T, Klappacher GW, Glogar D, Sperr WR, Grossschmidt K, Bankl H, Lechner K, Valent P Increase and redistribution of cardiac mast cells in auricular thrombosis. Possible role of kit ligand. Circulation 1995 91 275-283. 

Mast cell (MC), the high basal cardiac and serum histamine in Apo E k/o mice, along with the high number of cardiac mast cells, suggest possible ongoing cardiac mast cell activation that may participate in atherosclerosis (41). 

Huang M, Pang X, Letoumeau R, Boucher W, Theoharides TC. Acute stress induces cardiac mast cell activation and histamine release, effects that are increased in Apolipoprotein E knockout mice. Cardiovasc Res 2002 55 150-160. 

There are several possible routes whereby such responses can be affected. First, there is a neural response, as evidenced by the analogous symptoms of the cardiac and pulmonary chemoreflexes. Second, mediators released from the inflammatory cells in the lungs are carried by the blood directly to the heart. Of note, C3a and C5a which are released during anaphylaxis activate cardiac, but not limg mast cells (62). Third, antigens may penetrate the airway and alveolar epithelium and enter into the vasculature and directly interact with cardiac mast cells and basophils. This latter pathway is likely important when small molecules, such as sodium diisocyanate, are inhaled, as these molecules form albumin-isocyanate conjugates that may be related to the induction of toluene diisocyanate hypersensitivity (69). 

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