Abstract
Human mast cells, by elaborating various cytokines, chemokines and proinflammatory mediators play a complex role in several allergic and inflammatory disorders. Mast cells have been identified in human heart tissue in close proximity to the sarcolemma, in perivascular and adventitial locations and in the shoulder region of coronary atheroma. Human heart mast cells (HHMC) can be isolated from patients undergoing heart transplantation and can be immunologically activated in vitro to induce the release of tryptase, chymase, cysteinyl leukotriene C4 and prostaglandin D2. Several cytokines (e.g., stem cell factor and TNF-α) reside in secretory granules of HHMC. Mast cell density is increased in the hearts of patients with ischemic and idiopathic dilated cardiomyopathy. Cardiac mast cells might contribute to the evolution of atherosclerosis, dilated cardiomyopathy, cardiac and systemic anaphylaxis through the release of cytokines and vasoactive and proinflammatory mediators.
Similar content being viewed by others
REFERENCES
Marone, G. 1995. Human Basophils and Mast Cells in Health and Disease. Vol. I. Biological Aspects. Karger, Basel.
Marone, G. 1995. Human Basophils and Mast Cells in Health and Disease. Vol. II. Clinical Aspects. Karger, Basel.
Walsh, L. J., Trinchieri, G., Waldorf, H. A., Whitaker, D., and Murphy, G. F. 1991. Human dermal mast cells contain and release tumor necrosis factor α, which induces endothelial leukocyte adhesion molecule 1. Proc. Natl. Acad. Sci. USA 88:4220-4224.
Bradding, P., Feather, I. H., Howarth, P. H., Mueller, R., Roberts, J. A., Britten, K., Bews, J. P. A., Hunt, T. C., Okayama, Y., Heusser, C. H., Bullock, G. R., Church, M. K., and Holgate, S. T. 1992. Interleukin 4 is localized to and released by human mast cells. J. Exp. Med. 176:1381-1386.
Möller, A., Lippert, U., Lessmann, D., Kolde, G., Hamann, K., Welker, P., Schadendorf, D., Rosenbach, T., Luger, T., and Czarnetzki, B. M. 1993. Human mast cells produce IL-8. J. Immunol. 151:3261-3266.
Patella, V., Marinò, I., Arbustini, E., Lampärter-Schummert, B., Verga, L., Adt, M., and Marone, G. 1998. Stem cell factor in mast cells and increased cardiac mast cell density in idiopathic and ischemic cardiomyopathy. Circulation 97:971-978.
Rumsaeng, V., Cruikshank, W. W., Foster, B., Prussin, C., Kirshenbaum, A. S., Davis, T. A., Kornfeld, H., Center, D. M., and Metcalfe, D. D. 1997. Human mast cells produce the CD4+ T lymphocyte chemoattractant factor IL-16. J. Immunol. 159:2904-2910.
Yano, K., Yamaguchi, M., de Mora, F., Lantz, C. S, Butterfield, J. H., Costa, J. J., and Galli, S. J. 1997. Production of macrophage inflammatory protein-1α by human mast cells: increased anti-IgE-dependent secretion after IgE-dependent enhancement of mast cell IgE-binding ability. Lab. Invest. 77:185-193.
Marone, G., Casolaro, V., Cirillo, R., Stellato, C., and Genovese, A. 1989. Pathophysiology of human basophils and mast cells in allergic disorders. Clin. Immunol. Immunopathol. 50:S24-S40.
Galli, S. J. 1993. New concepts about the mast cell. New Engl. J. Med. 328:257-265.
Patella, V., Florio, G., and Marone, G. 1999. HIV-1 gp120 induces IL-4 and IL-13 release from human FcɛRI+ cells. Science, in press.
Marone, G. 1998. Asthma: recent advances. Immunol. Today 19:5-9.
Marone, G., de Crescenzo, G., Patella, V., and Genovese A. 1998. Human cardiac mast cells and their role in severe allergic reactions. Pages 237-257, in Marone, G., Austen, K. F., Holgate, S. T., Kay, A. B., and Lichtenstein, L. M. (eds.), Asthma and Allergic Diseases, Academic Press, New York.
de Paulis, A., Valentini, G., Spadaro, G., Lupoli, S., Tirri, G., and Marone, G. 1991. Human basophil releasability. VIII. Increased basophil releasability in patients with scleroderma. Arthritis Rheum. 34:1289-1296.
Patella, V., Marinò, I., Lampärter, B., Arbustini, E., Adt, M., and Marone, G. 1995. Human heart mast cells. Isolation, purification, ultrastructure, and immunologic characterization. J. Immunol. 154:2855-2865.
Patella, V., de Crescenzo, G., Ciccarelli, A., Marinò, I., Adt, M., and Marone, G. 1995. Human heart mast cells: a definitive case of mast cell heterogeneity. Int. Arch. Allergy Immunol. 106:386-393.
Patella, V., Marinò, I., Lampärter, B., Genovese, A., Adt, M., and Marone, G. 1995. Immunologic and non-immunologic release of histamine and tryptase from human heart mast cells. Inflammation Res. 44(S-I):S22-S23.
Marone, G., Patella, V., de Crescenzo, G., and Adt, M. 1995. Human heart mast cells in anaphylaxis and cardiovascular disease. Int. Arch. Allergy Immunol. 107:72-75.
Irani, A. A., Schechter, N. M., Craig, S. S., DeBlois, G., and Schwartz, L. B. 1986. Two types of human mast cells that have distinct neutral protease compositions. Proc. Natl. Acad. Sci. USA 83:4464-4468.
Schwartz, L. B., Lewis, R. A., Seldin, D., and Austen, K. F. 1981. Acid hydrolases and tryptase from secretory granules of dispersed human lung mast cells. J. Immunol. 126:1290-1294.
Schwartz, L. B., Riedel, C., Caulfield, J. P., Wasserman, S. I., and Austen, K. F. 1981. Cell association of complex of chymase, heparin proteoglycan and protein after degranulation by rat mast cells. J. Immunol. 126:2071-2078.
Marone, G., Triggiani, M., Cirillo, R., Giacummo, A., Hammarström, S., and Condorelli, M. 1986. IgE-mediated activation of human heart in vitro. Agents and Actions 18:194-196.
Kaartinen, M., Penttilä, A., and Kovanen, P. T. 1994. Accumulation of activated mast cells in the shoulder region of human coronary atheroma, the predilection site of atheromatous rupture. Circulation 90:1669-1678.
Kaartinen, M., Penttilä, A., Kovanen, P. T. 1994. Mast cells of two types differing in neutral protease composition in the human aortic intima. Demonstration of tryptase-and tryptase/chymase-containing mast cells in normal intimas, fatty streaks, and the shoulder region of atheromas. Arterioscler. Thromb. 14:966-972.
Urata, H., Kinoshita, A., Misono, K. S., Bumpus, F. M., and Husain, A. 1990. Identification of highly specific chymase as the major angiotensin II-forming enzyme in the human heart. J. Biol. Chem. 265:22348-22357.
Zeiher, A. M., Ihling, C., Pistorius, K., Schächinger, V., and Schaefer, H.-E. 1994. Increased tissue endothelin immunoreactivity in atherosclerotic lesions associated with acute coronary syndromes. Lancet 344:1405-1406.
Kokkonen, J. O., and Kovanen, P. T. 1989. Proteolytic enzymes of mast cell granules degrade low density lipoproteins and promote their granule-mediated uptake by macrophages in vitro. J. Biol. Chem. 264:10749-10755.
Hattori, Y., and Levi, R. 1986. Effect of PGD2 on cardiac contractility: a negative inotropism secondary to coronary vasoconstriction conceals a primary positive inotropic action. J. Pharm. Exp. Ther. 237:719-724.
Marone, G., Giordano, A., Cirillo, R., Triggiani, M., and Vigorito, C. 1988. Cardiovascular and metabolic effects of peptide leukotrienes in man. Ann. N. Y. Acad. Sci. 524:321-333.
Vigorito, C., Marone, G., and Condorelli, M. 1988. Cardiovascular effects of histamine and sulfidopeptide leukotrienes. Pages 107-123, in Marone, G., Lichtenstein, L. M., Condorelli, M., and Fauci, A. S. (eds.), Human Inflammatory Disease. Clinical Immunology. Vol. I, BC Decker Inc., Toronto, Philadelphia.
Vigorito, C., Giordano, A., Cirillo, R., Genovese, A., Rengo, F., and Marone, G. 1997. Metabolic and hemodynamic effects of peptide leukotriene C4 and D4 in man. Int. J. Clin. Lab. Res. 27:178-184.
Marone, G., Casolaro, V., Paganelli, R., and Quinti, I. 1989. IgG anti-IgE from atopic dermatitis induces mediator release from basophils and mast cells. J. Invest. Dermatol. 93:246-252.
Hide, M., Francis, D. M., Grattan, C. E. H., Hakimi, J., Kochan, J. P., and Greaves, M. W. 1993. Autoantibodies against the high-affinity IgE receptor as a cause of histamine release in chronic urticaria. N. Engl. J. Med. 328:1599-1604.
Marone, G., Spadaro, G., Palumbo, C., and Condorelli, G. 1999. The anti-IgE/anti-FcɛRIα autoantibody network in allergic and autoimmune diseases. Clin. Exp. Allergy 29:17-27.
Schäfer, H., Mathey, D., Hugo, F., and Bhakdi, S. 1986. Deposition of the terminal C5b-9 complement complex in infarcted areas of human myocardium. J. Immunol. 137:1945-1949.
Crawford, M. H., Grover, F. L., Kolb, W. P., McMahan, C. A., O'Rourke, R. A., McManus, L. M., and Pinckard, R. N. 1988. Complement and neutrophil activation in the pathogenesis of ischemic myocardial injury. Circulation 78:1449-1458.
Weisman, H. F., Bartow, T., Leppo, M. K., Marsh, H. C. Jr., Carson, G. R., Concino, M. F., Boyle, M. P., Roux, K. H., Weisfeldt, M. L., and Fearon, D. T. 1990. Soluble human complement receptor type 1: in vivo inhibitor of complement suppressing postischemic myocardial inflammation and necrosis. Science 249:146-151.
Shandelya, S. M. L., Kuppusamy, P., Herskowitz, A., Weisfeldt, M. L., and Zweier, L. 1993. Soluble complement receptor type 1 inhibits the complement pathway and prevents contractile failure in the postischemic heart. Evidence that complement activation is required for neutrophil-mediated reperfusion injury. Circulation 88:2812-2826.
Ito, B. R., Engler, R. L., and del Balzo, U. 1993. Role of cardiac mast cells in complement C5a-induced myocardial ischemia. Am. J. Physiol. 264:H1346-H1354.
del Balzo, U., Polley, M. J., and Levi, R. 1989. Cardiac anaphylaxis. Complement activation as an amplification system. Circulation Res. 65:847-857.
Smith, P. L., Kagey-Sobotka, A., Bleecker, E. R., Traystman, R., Kaplan, A. P., Gralnick, H., Valentine, M. D., Permutt, S., and Lichtenstein, L. M. 1980. Physiologic manifestations of human anaphylaxis. J. Clin. Invest. 66:1072-1080.
Schulman, E. S., Post, T. J., Henson, P. M., and Giclas, P. 1988. Differential effects of the complement peptides, C5a and C5a des Arg on human basophil and lung mast cell histamine release. J. Clin. Invest. 81:918-923.
Tsai, M., Shih, L. S., Newlands, G. F. J., Takeishi, T., Langley, K. E., Zsebo, K. M., Miller, H. R. P., Geissler, E. N., and Galli, S. J. 1991. The rat c-kit ligand, stem cell factor, induces the development of connective tissue-type and mucosal mast cells in vivo. Analysis by anatomical distribution, histochemistry, and protease phenotype. J. Exp. Med. 174:125-131.
Columbo, M., Horowitz, E. M., Botana, L. M., MacGlashan, D. W. Jr., Bochner, B. S., Gillis, S., Zsebo, K. M., Galli, S. J., and Lichtenstein, L. M. 1992. The human recombinant c-kit receptor ligand, rhSCF, induces mediator release from human cutaneous mast cells and enhances IgE-dependent mediator release from both skin mast cells and peripheral blood basophils. J. Immunol. 149:599-608.
de Paulis, A., Ciccarelli, A., Cirillo, R., de Crescenzo, G., Columbo, M., and Marone, G. 1992. Modulation of human lung mast cell function by the c-kit receptor ligand. Int. Arch. Allergy Immunol. 99:326-329.
Stellato, C., Cirillo, R., de Paulis, A., Casolaro, V., Patella, V., Mastronardi, P., Mazzarella, B., and Marone, G. 1992. Human basophil/mast cell releasability. IX. Heterogeneity of the effects of opioids on mediator release. Anesthesiology 77:932-940.
Stellato, C., de Crescenzo, G., Patella, V., Tatangelo, F., Mastronardi, P., Mazzarella, B., and Marone, G. 1996. Human basophil/mast cell releasability. XI. Heterogeneity of mediator release from human basophils and mast cells induced by contrast media (CM). J. Allergy Clin. Immunol. 97:838-850.
Adt, M., Patella, V., Marinò, I., Lamparter, B., and Marone, G. 1994. Immunologic characterization of human heart mast cells. J. Invest. Dermatol. 103:621.
Bankl, H. C., Radaszkiewicz, T., Klappacher, G. W., Glogar, D., Sperr, W. R., Groβschmidt, K., Bankl, H., Lechner, K., and Valent, P. 1995. Increase and redistribution of cardiac mast cells in auricular thrombosis. Possible role of kit ligand. Circulation 91:275-283.
Kitamura, Y., Taguchi, T., Yokoyama, M., Inoue, M., Yamatodani, A., Asano, H., Koyama, T., Kanamaru, A., Hatanaka, K., and Wershil, B. K. 1986. Higher susceptibility of mast-cell-deficient W/Wv mutant mice to brain thromboembolism and mortality caused by intravenous injection of India ink. Am. J. Pathol. 122:469-480.
Kauhanen, P., Kovanen, P. T., Reunala, T., and Lassila, R. 1998. Effects of skin mast cells on bleeding time and coagulation activation at the site of platelet plug formation. Thromb. Haemost. 79:843-847.
Pejler, G., Söderström, K., and Karlström, A. 1994. Inactivation of thrombin by a complex between rat mast-cell protease I and heparin proteoglycan. Biochem. J. 299:507-513.
Schwartz, L. B., Bradford, T. R., Littman, B. H., and Wintroub, B. U. 1985. The fibrinogenolytic activity of purified tryptase from human lung mast cells. J. Immunol. 135:2762-2767.
Maier, M., Spragg, J., and Schwartz, L. B. 1983. Inactivation of human high molecular weight kininogen by mast cell tryptase. J. Immunol. 130:2352-2356.
Sillaber, C., Bahgestanian, M., Bevec, D., Willheim, M., Agis, H., Kapiotis, S., Füreder, W., Bankl, H. C., Kiener, H. P., Speiser, W., Binder, B. R., Lechner, K., and Valent, P. 1999. The mast cell as site of tissue-type plasminogen activator expression and fibrinolysis. J. Immunol. 162:1032-1041.
Bernreiter, M. 1959. Electrocardiogram of patient in anaphylactic shock. J.A.M.A. 170:1628-1630.
Booth, B. H., and Patterson, R. 1970. Electrocardiographic changes during human anaphylaxis. J.A.M.A. 211:627-631.
Stellato, C., and Marone, G. 1995. The role of basophils and mast cells in adverse reactions to drugs used during general anesthesia. Pages 108-131, in Marone, G. (ed.), Human Basophils and Mast Cells in Health and Disease. Vol. II. Clinical Aspects, Karger, Basel.
Ross, R. 1999. Atherosclerosis: an inflammatory disease. N. Engl. J. Med. 340:115-126.
Hjelmman, G. 1952. Über das erste Auftreten der Mastzellen in einigen Geweben und Organen bei Homoembryonen mit Berücksichtigung der Zunahme dieser Zellen während der Embryonalentwicklung. Soc. Sci. Fenn. Comm. Biol. 13:1-53.
Pollack, O. J. 1957. Mast cells in the circulatory system of man. Circulation 1084-1089.
Pomerance, A. 1958. Peri-arterial mast cells in coronary atheroma and thrombosis. J. Pathol. Bacteriol. 76:55-70.
Forman, M. B., Oates, J. A., Robertson, D., Robertson, R. M., Roberts, L. J., and Virmani, R. 1985. Increased adventitial mast cells in a patient with coronary spasm. N. Engl. J. Med. 313:1138-1141.
Kolodgie, F. D., Virmani, R., Cornhill, J. F., Herderick, E. E., and Smialek, J. 1991. Increase in atherosclerosis and adventitial mast cells in cocaine abusers: an alternative mechanism of cocaine-associated coronary vasospasm and thrombosis. J. Am. Coll. Cardiol. 17:1553-1560.
Kalsner, S., and Richards, R. 1984. Coronary arteries of cardiac patients are hyperactive and contain stores of amines: a mechanism for coronary spasm. Science 223:1435-1436.
Vigorito, C., Poto, S., Picotti, G. B., Triggiani, M., and Marone, G. 1986. Effect of activation of the H1 receptor on coronary hemodynamics in man. Circulation 73:1175-1182.
Constantinides, P. 1953. Mast cells and susceptibility to experimental atherosclerosis. Science 117:505-506.
Bloom, G. D. 1984. A short history of the mast cell. Acta Otolaryngol. 414(Suppl.):87-92.
Kovanen, P. T. 1993. The mast cell: a potential link between inflammation and cellular cholesterol deposition in atherogenesis. Europ. Heart J. 14(Suppl. K):105-117.
Kovanen, P. T. 1995. Role of mast cells in atherosclerosis. Pages 132-170, in Marone, G. (ed.), Human Basophils and Mast Cells in Health and Disease. Vol II. Clinical Aspects, Karger, Basel.
Kovanen, P. T., Kaartinen, M., and Paavonen, T. 1995. Infiltrates of activated mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction. Circulation 92:1084-1088.
Kokkonen, J. O., and Kovanen, P. T. 1987. Stimulation of mast cells leads to cholesterol accumulation in macrophages in vitro by a mast cell granule-mediated uptake of low density lipoprotein. Proc. Natl. Acad. Sci. USA 84:2287-2291.
Lindstedt, K. A., Kokkonen, J. O., and Kovanen, P. T. 1992. Soluble heparin proteoglycans released from stimulate mast cells induce uptake of low density lipoproteins by macrophages via scavenger receptor-mediated phagocytosis. J. Lipid. Res. 33:65-75.
Kaartinen, M., Penttilä, A., and Kovanen, P. T. 1996. Mast cells in rupture-prone areas of human coronary atheromas produce and store TNF-α. Circulation 94:2787-2792.
Frangogiannis, N. G., Perrard, J. L., Mendoza, L. H., Burns, A. R., Lindsey, M. L., Ballantyne, C. M., Michael, L. H., Smith, C. W., and Entman, M. L. 1998. Stem cell factor induction is associated with mast cell accumulation after canine myocardial ischemia and reperfusion. Circulation 98:687-698.
Frangogiannis, N. G., Lindsey, M. L., Michael, L. H., Youker, K. A., Bressler, R. B., Mendoza, L. H., Spengler, R. N., Smith, C. W., and Entman, M. L. 1998. Resident cardiac mast cells degranulate and release preformed TNF-α, initiating the cytokine cascade in experimental canine myocardial ischemia/reperfusion. Circulation 98:699-710.
Estensen, R. D. 1984. Eosinophilic myocarditis: a role for mast cells? Arch. Pathol. Lab. Med. 108:358-359.
Hiruta, Y., Adachi, K., Omamoto, T., Fujiura, Y., and Toshima, H. 1991. Cardiac mast cells in myocardial diseases (in Japanese). Kokyu To Junkan 39:1133-1138.
Tai, P.-C., Spry, C. J. F., Olsen, E. G. J., Ackerman, S. J., Dunnette, S., and Gleich, G. J. 1987. Deposits of eosinophil granule proteins in cardiac tissues of patients with eosinophilic endomyocardial disease. Lancet 1:643-647.
Desreumax, P., Janin, A., Dubucquoi, S., Copin, M.-C., Torpier, G., Capron, A., Capron, M., and Prin, L. 1993. Synthesis of interleukin-5 by activated eosinophils in patients with eosinophilic heart diseases. Blood 82:1553-1560.
Patella, V., de Crescenzo, G., Marinò, I., Genovese, A., Adt, M., Gleich, G. J., and Marone, G. 1996. Eosinophil granule proteins activate human heart mast cells. J. Immunol. 157:129-1225.
Okayama, Y., El-Lati, S. G., Leiferman, K. M., and Church, M. K. 1994. Eosinophil granule proteins inhibit substance P-induced histamine release from human skin mast cells. J. Allergy Clin. Immunol. 93:900-909.
Mukherjee, D., and Sen, S. 1991. Alteration of collagen phenotypes in ischemic cardiomyopathy. J. Clin. Invest. 88:1141-1146.
Seibold, J. R., Giorno, R. C., and Claman, H. N. 1990. Dermal mast cells degranulation in systemic sclerosis. Arthritis Rheum. 33:1702-1709.
Fox, C. C., Lazenby, A. J., Moore, W. C., Yardley, J. H., Bayless, T. M., and Licthenstein, L. M. 1990. Enhancements of human intestinal mast cell mediator release in active ulcerative colitis. Gastroenterology 99:119-124.
Kawanami, O., Ferrans, V. J., Fulmer, J. D., and Crystal, R. G. 1979. Ultrastructure of pulmonary mast cells in patients with fibrotic lung disorders. Lab. Invest. 40:717-734.
Broide, D. H., Smith, C. M., and Wasserman, S. I. 1990. Mast cells and pulmonary fibrosis. Identification of a histamine releasing factor in bronchoalveolar lavage fluid. J. Immunol. 145:1838-1844.
Fernex, M. 1968. The mast-cell system. Its relationship to atherosclerosis, fibrosis and eosinophils. The Williams & Wilkins Co., Baltimore.
Fauci, A. S., Harley, J. B., Roberts, W. C., Ferrans, V. J., Gralnic, H. R., and Björnson, B. H. 1982. The idiopathic hypereosinophilic syndrome. Clinical, pathophysiologic and therapeutic considerations. Ann. Intern. Med. 87:78-92.
Lichtbroun, A. S., Sandhaus, L. M., Giorno, R. C., Kim, H., and Seibold, J. R. 1990. Myocardial mast cells in systemic sclerosis. A report of three fatal cases. Am. J. Med. 89:372-376.
Hatamochi, A., Fujiwara, K., and Ueki, H. 1985. Effects of histamine on collagen synthesis by cultured fibroblasts derived from guinea pig skin. Arch. Dermatol. Res. 277:60-64.
Baud, L., Perez, J., Denis, M., and Ardaillou, R. 1987. Modulation of fibroblast proliferation by sulfidopeptide leukotrienes: effect of indomethacin. J. Immunol. 138:1190-1195.
Ruoss, S. J., Hartmann, T., and Caughey, G. H. 1991. Mast cell tryptase is a mitogen for cultured fibroblasts. J. Clin. Invest. 88:493-499.
Valent, P., Spanblöchl, E., Sperr, W. R., Sillaber, C., Zsebo, K. M., Agis, H., Strobl, H., Geissler, K., Bettelheim, P., and Lechner, K. 1992. Induction of differentiation of human mast cells from bone marrow and peripheral blood mononuclear cells by recombinant human stem cell factor/kit ligand in long term culture. Blood 80:2237-2245.
Saito, H., Sakaguchi, N., Matsumoto, K., Tsubaki, T., Numazaki, T., Ebisawa, M., Kobayashi, M., Ozawa, R., Yanagi, H., Akasawa, A., and Iikura, Y. 1994. Growth in methylcellulose of human mast cells in hematopoietic colonies stimulated by steel factor, a c-kit ligand. Int. Arch. Allergy Immunol. 103:143-151.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Marone, G., de Crescenzo, G., Florio, G. et al. Immunological Modulation of Human Cardiac Mast Cells. Neurochem Res 24, 1195–1202 (1999). https://doi.org/10.1023/A:1020776807187
Issue Date:
DOI: https://doi.org/10.1023/A:1020776807187