Abstract
Myocardial infarction is associated with an acute inflammatory response, leading to replacement of injured cardiomyocytes with granulation tissue. Mast cells are actively involved in postinfarction inflammation by releasing histamine and tumor necrosis factor-α, triggering a cytokine cascade. During the proliferative phase of healing, mast cells accumulate in the infarct and may regulate fibrous tissue deposition and angiogenesis by releasing growth factors, angiogenic mediators, and proteases. This chapter describes simple and reliable methods used to identify mast cells in control and infarcted canine hearts. Toluidine blue staining, labeling with conjugated avidin, and tryptase histochemistry are useful in the detection of mast cells in canine tissues. In the healing infarct, mast cells are associated with other cell types that are important for granulation tissue formation. We present immunohistochemical methods identifying monocytes, neutrophils, macrophages, endothelial cells, myofibroblasts, and smooth muscle cells in dog infarcts. These techniques are useful tools for pathological studies in canine models.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Patella, V., Marino, I., Arbustini, E., et al. (1998) Stem cell factor in mast cells and increased mast cell density in idiopathic and ischemic cardiomyopathy. Circulation 97, 971–978.
Frangogiannis, N. G., Burns, A. R., Michael, L. H., and Entman, M. L. (1999) Histochemical and morphological characteristics of canine cardiac mast cells. Histochem. J. 31, 221–229.
Gersch, C., Dewald, O., Zoerlein, M., Michael, L. H., Entman, M. L., and Frangogiannis, N. G. (2002) Mast cells and macrophages in normal C57/BL/6 mice. Histochem. Cell Biol. 118, 41–49.
Gordon, J. R. and Galli, S. J. (1990) Mast cells as a source of both preformed and immunologically inducible TNF-alpha/cachectin. Nature 346, 274–276.
Plaut, M., Pierce, J. H., Watson, C. J., Hanley-Hyde, J., Nordan, R. P., and Paul, W. E. (1989) Mast cell lines produce lymphokines in response to cross-linkage of Fc epsilon RI or to calcium ionophores. Nature 339, 64–67.
Baghestanian, M., Hofbauer, R., Kiener, H. P., et al. (1997) The c-kit ligand stem cell factor and anti-IgE promote expression of monocyte chemoattractant protein-1 in human lung mast cells. Blood 90, 4438–4449.
Rumsaeng, V., Vliagoftis, H., Oh, C. K., and Metcalfe, D. D. (1997) Lymphotactin gene expression in mast cells following Fc(epsilon) receptor I aggregation: modulation by TGF-beta, IL-4, dexamethasone, and cyclosporin A. J. Immunol. 158, 1353–1360.
Kaartinen, M., Penttila, A., and Kovanen, P. T. (1996) Mast cells in rupture-prone areas of human coronary atheromas produce and store TNF-alpha. Circulation 94, 2787–2792.
Frangogiannis, N. G., Lindsey, M. L., Michael, L. H., et al. (1998) Resident cardiac mast cells degranulate and release preformed TNF-alpha, initiating the cytokine cascade in experimental canine myocardial ischemia/reperfusion. Circulation 98, 699–710.
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.
Linden, J. (1994) Cloned adenosine A3 receptors: pharmacological properties, species differences and receptor functions. Trends Pharmacol. Sci. 15, 298–306.
Frangogiannis, N. G., Smith, C. W., and Entman, M. L. (2002) The inflammatory response in myocardial infarction. Cardiovasc. Res. 53, 31–47.
Pennington, D. W., Lopez, A. R., Thomas, P. S., Peck, C., and Gold, W. M. (1992) Dog mastocytoma cells produce transforming growth factor beta 1. J. Clin. Invest. 90, 35–41.
Qu, Z., Liebler, J. M., Powers, M. R., et al. (1995) Mast cells are a major source of basic fibroblast growth factor in chronic inflammation and cutaneous hemangioma. Am. J. Pathol. 147, 564–573.
Boesiger, J., Tsai, M., Maurer, M., et al. (1998) Mast cells can secrete vascular permeability 3factor/vascular endothelial cell growth factor and exhibit enhanced release after immunoglobulin E-dependent upregulation of fc epsilon receptor I expression. J. Exp. Med. 188, 1135–1145.
Shiota, N., Rysa, J., Kovanen, P. T., Ruskoaho, H., Kokkonen, J. O., and Lindstedt, K. A. (2003) A role for cardiac mast cells in the pathogenesis of hypertensive heart disease. J. Hypertens. 21, 1935–1944.
Brower, G. L., Chancey, A. L., Thanigaraj, S., Matsubara, B. B., and Janicki, J. S. (2002) Cause and effect relationship between myocardial mast cell number and matrix metalloproteinase activity. Am. J. Physiol. Heart Circ. Physiol. 283, H518–H525.
Chancey, A. L., Brower, G. L., and Janicki, J. S. (2002) Cardiac mast cell-mediated activation of gelatinase and alteration of ventricular diastolic function. Am. J. Phtysiol. Heart Circ. Physiol. 282, H2152–H2158.
Fang, K. C., Wolters, P. J., Steinhoff, M., Bidgol, A., Blount, J. L., and Caughey, G. H. (1999) Mast cell expression of gelatinases A and B is regulated by kit ligand and TGF-beta. J. Immunol. 162, 5528–5535.
Matsumoto, T., Wada, A., Tsutamoto, T., Ohnishi, M., Isono, T., and Kinoshita, M. (2003) Chymase inhibition prevents cardiac fibrosis and improves diastolic dysfunction in the progression of heart failure. Circulation 107, 2555–2558.
Bergstresser, P. R., Tigelaar, R. E., and Tharp, M. D. (1984) Conjugated avidin identifies cutaneous rodent and human mast cells. J. Invest. Dermatol. 83, 214–218.
Caughey, G. H., Viro, N. F., Calonico, L. D., McDonald, D. M., Lazarus, S. C., and Gold, W. M. (1988) Chymase and tryptase in dog mastocytoma cells: asynchronous expression as revealed by enzyme cytochemical staining. J. Histochem. Cytochem. 36, 1053–1060.
Beckstead, J. H. (1994) A simple technique for preservation of fixation-sensitive antigens in paraffin-embedded tissues. J. Histochem. Cytochem. 42, 1127–1134.
Zeng, L., Takeya, M., Ling, X., Nagasaki, A., and Takahashi, K. (1996) Interspecies reactivities of anti-human macrophage monoclonal antibodies to various animal species. J. Histochem. Cytochem. 44, 845–853.
Hawkins, H. K., Entman, M. L., Zhu, J. Y., et al. (1996) Acute inflammatory reaction after myocardial ischemic injury and reperfusion. Development and use of a neutrophil-specific antibody. Am. J. Pathol. 148, 1957–1969.
Enerback, L. (1966) Mast cells in rat gastrointestinal mucosa. I. Effects of fixation. Acta Pathol. Microbiol. Scand. 66, 289–302.
Enerback, L. (1966) Mast cells in rat gastrointestinal mucosa. 2. Dye-binding and metachromatic properties. Acta Pathol. Microbiol. Scand. 66, 303–312.
Miller, J. S. and Schwartz, L. B. (1989) Human mast cell proteases and mast cell heterogeneity. Curr. Opin. Immunol. 1, 637–642.
Tharp, M. D., Seelig, L. L., Jr., Tigelaar, R. E., and Bergstresser, P. R. (1985) Conjugated avidin binds to mast cell granules. J. Histochem. Cytochem. 33, 27–32.
Frangogiannis, N. G., Mendoza, L. H., Ren, G., et al. (2003) MCSF expression is induced in healing myocardial infarcts and may regulate monocyte and endothelial cell phenotype. Am. J. Physiol. Heart Circ. Physiol. 285, H483–H492.
Ren, G., Michael, L. H., Entman, M. L., and Frangogiannis, N. G. (2002) Morphological characteristics of the microvasculature in healing myocardial infarcts. J. Histochem. Cytochem. 50, 71–79.
Frangogiannis, N. G., Shimoni, S., Chang, S. M., et al. (2002) Evidence for an active inflammatory process in the hibernating human myocardium. Am. J. Pathol. 160, 1425–1433.
Frangogiannis, N. G., Michael, L. H., and Entman, M. L. (2000) Myofibroblasts in reperfused myocardial infarcts express the embryonic form of smooth muscle myosin heavy chain (SMemb). Cardiovasc. Res. 48, 89–100.
Acknowledgments
The authors wish to thank Sharon Malinowski and Connie Mata for editorial assistance with the manuscript. This work was supported by NIH Grant HL-42550, a Grant-in-Aid from the American Heart Association Texas Affiliate, and the DeBakey Heart Center.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Humana Press Inc.
About this protocol
Cite this protocol
Frangogiannis, N.G., Entman, M.L. (2006). Identification of Mast Cells in the Cellular Response to Myocardial Infarction. In: Krishnaswamy, G., Chi, D.S. (eds) Mast Cells. Methods in Molecular Biology, vol 315. Humana Press. https://doi.org/10.1385/1-59259-967-2:091
Download citation
DOI: https://doi.org/10.1385/1-59259-967-2:091
Publisher Name: Humana Press
Print ISBN: 978-1-58829-374-9
Online ISBN: 978-1-59259-967-7
eBook Packages: Springer Protocols