Mast Cells in Experimental Myocardial Infarction

  • Nikolaos G. Frangogiannis
  • Mark L. Entman
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 248)


Myocardial infarction is associated with an inflammatory reaction, which is a prerequisite for healing and scar formation 1-3 Myocardial cell necrosis results in the release of subcellular membrane constituents, rich in mitochondria, which are capable of activating the complement cascade.4,5 This represents the initial chemotactic event responsible for neutrophil influx in the ischemic myocardium. Subsequently, activated neutrophils adhere to the endothelium and transmigrate to the extravascular space. Neutrophils accumulating in the ischemic areas release proteolytic enzymes or reactive oxygen species, injuring surrounding myocytes. However, in vivo, these toxic products are almost exclusively secreted by adherent neutrophils. Neutrophil adhesion to cardiac myocytes is dependent on neutrophil integrin activation and on the induction of Intercellular Adhesion Molecule-I (ICAM-I) on cardiac myocytes.6-8 Myocyte ICAM-1 induction is dependent on a cytokine cascade leading to IL-6 expression in mononuclear cells9 and myocytes.1O Cardiac mast cells appear to have a significant role in initiating this cytokine cascade,9 and may also serve as important sources of fibrogenic factors during healing of a reperfused myocardial infarct.11


Mast Cell Stem Cell Factor Mast Cell Degranulation Human Mast Cell Experimental Myocardial Infarction 
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  1. 1.
    Frangogiannis NG, Smith CW, Entman ML. The Inflammatory Response in Myocardial Infarction. Cardiovasc Res 2002;53:31–47.PubMedCrossRefGoogle Scholar
  2. 2.
    Frangogiannis NG, Youker KA, Rossen RD, et al. Cytokines and the Microcirculation in Ischemia and Reperfusion. J Mol Cell Cardiol 1998;30:2567–2576.PubMedCrossRefGoogle Scholar
  3. 3.
    Mehta JL, Li DY. Inflammation in Ischemic Heart Disease: Response to Tissue Injury or a Pathogenetic Villain? Cardiovasc Res 1999;43:291–299.Google Scholar
  4. 4.
    Rossen RD, Michael LH, Hawkins HK, et al. Cardiolipin-Protein Complexes and Initiation of Complement Activation after Coronary Artery Occlusion. Circ Res 1994;75:546–555.PubMedCrossRefGoogle Scholar
  5. 5.
    Kagiyama A, Savage HE, Michael LH, et al. Molecular Basis of Complement Activation in Ischemic Myocardium: Identification of Specific Molecules of Mitochondrial Origin that Bind Human Clq and Fix Complement. Circ Res 1989;64:607–615.PubMedCrossRefGoogle Scholar
  6. 6.
    Entman ML, Youker K, Shappell SB, et al. Neutrophil Adherence to Isolated Adult Canine Myocytes. Evidence for a CD18-Dependent Mechanism. J Clin Invest 1990;85:1497–1506.PubMedCrossRefGoogle Scholar
  7. 7.
    Entman ML, Michael L, Rossen RD, et al. Inflammation in the Course of Early Myocardial Ischemia. FASEB J 1991;5:2529–2537.PubMedGoogle Scholar
  8. 8.
    Entman ML, Youker K, Shoji T, et al. Neutrophil Induced Oxidative Injury of Cardiac Myocytes. A Compartmented System Requiring CD11b/CD18-ICAM-1 Adherence. J Clin Invest 1992;90:1335–1345.PubMedCrossRefGoogle Scholar
  9. 9.
    Frangogiannis NG, Lindsey ML, Michael LH, et al. Resident Cardiac Mast Cells Degranulate and Release Preformed TNF- Alpha, Initiating the Cytokine Cascade in Experimental Canine Myocardial Ischemia/Reperfusion. Circulation 1998;98:699–710.PubMedCrossRefGoogle Scholar
  10. 10.
    Gwechenberger M, Mendoza, LH, Youker KA, et al. Cardiac Myocytes Produce Interleukin-6 in Culture and in Viable Border Zone of Reperfused Infarctions. Circulation 1999;99:546–551.PubMedCrossRefGoogle Scholar
  11. 11.
    Frangogiannis NG, Perrard JL, Mendoza L H, et al. Stem Cell Factor Induction is Associated with Mast Cell Accumulation after Canine Myocardial Ischemia and Reperfusion. Circulation 1998;98:687–698.PubMedCrossRefGoogle Scholar
  12. 12.
    Metcalfe DD, Baram D, Mekori YA. Mast Cells. Physiol Rev 1997;77:1033–1079.Google Scholar
  13. 13.
    Enerback L. Mast Cells in Rat Gastrointestinal Mucosa. I. Effects of Fixation. Acta Pathol Microbiol Scand 1966;66:289–302.PubMedGoogle Scholar
  14. 14.
    Irani AM, Schwartz LB. Human Mast Cell Heterogeneity. Allergy Proc 1994;15:303–308.PubMedCrossRefGoogle Scholar
  15. 15.
    Patella V, de Crescenzo G, Ciccarelli A, et al. Human Heart Mast Cells: A Definitive Case of Mast Cell Heterogeneity. Int Arch Allergy Immunol 1995;106:386–393.PubMedCrossRefGoogle Scholar
  16. 16.
    Patella V, Marino I, Arbustini E, et al. Stem Cell Factor in Mast Cells and Increased Mast Cell Density in Idiopathic and Ischemic Cardiomyopathy. Circulation 1998;97:971–978.PubMedCrossRefGoogle Scholar
  17. 17.
    Frangogiannis NG, Shimoni S, Chang SM., et al. Evidence for an Active Inflammatory Process in the Hibernating Human Myocardium. Am J Pathol 2002;160:1425–1433.PubMedCrossRefGoogle Scholar
  18. 18.
    Forman MB, Oates JA, Robertson D, et al. Increased Adventitial Mast Cells in a Patient with Coronary Spasm. N Engl J Med 1985;313:1138–1141.PubMedCrossRefGoogle Scholar
  19. 19.
    Hara M, Ono K, Hwang MW, et al. Evidence for a Role of Mast Cells in the Evolution to Congestive Heart Failure. J Exp Med 2002;195:375–381.PubMedCrossRefGoogle Scholar
  20. 20.
    Laine P, Kaartinen M, Penttila A, et al. Association Between Myocardial Infarction and the Mast Cells in the Adventitia of the Infarct-Related Coronary Artery. Circulation 1999;99:361–369.PubMedCrossRefGoogle Scholar
  21. 21.
    Ito BR, Engler RL, del Balzo U. Role of Cardiac Mast Cells in Complement C5a- Induced Myocardial Ischemia. Am J Physiol 1993;264:H1346–H1354.PubMedGoogle Scholar
  22. 22.
    Sperr WR, Bankl HC, Mundigler G, et al. The Human Cardiac Mast Cell: Localization, Isolation, Phenotype, and Functional Characterization. Blood 1994;84:3876–3884.PubMedGoogle Scholar
  23. 23.
    Patella V Marino I, Lamparter B, et al. Human Heart Mast Cells. Isolation, Purification, Ultrastructure, and Immunologic Characterization. J Immunol 1995;154:2855–2865.PubMedGoogle Scholar
  24. 24.
    Rakusan K, Sarkar K, Turek Z, et al. Mast Cells in the Rat Heart During Normal Growth and in Cardiac Hypertrophy. Circ Res 1990;66:511–516.PubMedCrossRefGoogle Scholar
  25. 25.
    Gersch C, Dewald O, Zoerlein M, et al. Mast Cells and Macrophages in C57/BL/6 Mice. Histochem Cell Biol 2002;118:41–49.PubMedGoogle Scholar
  26. 26.
    Frangogiannis NG, Burns AR, Michael LH, et al. Histochemical and Morphological Characteristics of Canine Cardiac Mast Cells. Histochem J 1999;31:221–229.PubMedCrossRefGoogle Scholar
  27. 27.
    Gordon JR, Burd PR, Galli SJ. Mast Cells as a Source of Multifunctional Cytokines. Immunol Today 1990;11:458–464.PubMedCrossRefGoogle Scholar
  28. 28.
    Gordon JR, Galli SJ. Mast Cells as a Source of Both Preformed and Immunologically Inducible TNF-Alpha/Cachectin. Nature 1990;346:274–276.PubMedCrossRefGoogle Scholar
  29. 29.
    Boesiger J, Tsai M, Maurer M, et al. Mast Cells Can Secrete Vascular Permeability Factor/ Vascular Endothelial Cell Growth Factor and Exhibit Enhanced Release After Immunoglobulin E-Dependent Upregulation of fc Epsilon Receptor I Expression. J Exp Med 1998;188:1135–1145.PubMedCrossRefGoogle Scholar
  30. 30.
    Kaartinen M, Penttila A, and Kovanen PT. Mast Cells in Rupture-Prone Areas of Human Coronary Atheromas Produce and Store TNF-Alpha. Circulation 1996;94:2787–2792.PubMedCrossRefGoogle Scholar
  31. 31.
    Kanwar S, Kubes P. Mast Cells Contribute to Ischemia/Reperfusion-Induced Granulocyte Infiltration and Intestinal Dysfunction. Am J Physiol 1994;267:G316–G321.PubMedGoogle Scholar
  32. 32.
    Cerniway RJ, Yang Z, Jacobson MA, et al. Targeted Deletion of A(3) Adenosine Receptors Improves Tolerance to Ischemia-Reperfusion Injury in Mouse Myocardium. Am J Physiol Heart Circ Physiol 2001;281:H1751–H1758.PubMedGoogle Scholar
  33. 33.
    Geng J G, Bevilacqua MP, Moore KL, et al. Rapid Neutrophil Adhesion to Activated Endothelium Mediated by GMP-140. Nature 1990;343:757–760.PubMedCrossRefGoogle Scholar
  34. 34.
    Inoue Y, King TE Jr, Tinkle SS, et al. Human Mast Cell Fibroblast Growth Factor in Pulmonary Fibrotic Disorders. Am J Pathol 1996;149:2037–2054.PubMedGoogle Scholar
  35. 35.
    Hawkins RA, Claman HN, Clark RA, et al. Increased Dermal Mast Cell Populations in Progressive Systemic Sclerosis: A Link in Chronic Fibrosis? Ann Intern Med 1985;102:182–186.PubMedGoogle Scholar
  36. 36.
    Rottem M, Okada T, Goff JP, et al. Mast Cells Cultured from the Peripheral Blood of Normal Donors and Patients with Mastocytosis Originate from a CD34+/Fc Epsilon RI- Cell Population. Blood 1994;84:2489–2496.PubMedGoogle Scholar
  37. 37.
    Rodewald HR, Dessing M, Dvorak AM, et al. Identification of a Committed Precursor for the Mast Cell Lineage. Science 1996;271:818–822.PubMedCrossRefGoogle Scholar
  38. 38.
    Galli SJ, Tsai M, Wershil BK. The C-Kit Receptor, Stem Cell Factor, and Mast Cells. What Each is Teaching Us About the Others. Am J Pathol 1993;142:965–974.PubMedGoogle Scholar
  39. 39.
    Meininger CJ, Yano H, Rottapel R, et al. The C-Kit Receptor Ligand Functions as a Mast Cell Chemoattractant. Blood 1992;79:958–963.PubMedGoogle Scholar
  40. 40.
    Galli SJ, Iemura A, Garlick DS, et al. Reversible Expansion of Primate Mast Cell Populations In Vivo by Stem Cell Factor. J Clin.Invest 1993;91:148–152.PubMedCrossRefGoogle Scholar
  41. 41.
    Iemura A, Tsai M, Ando A, et al. The C-Kit Ligand, Stem Cell Factor, Promotes Mast Cell Survival by Suppressing Apoptosis. Am J Pathol 1994;144:321–328.PubMedGoogle Scholar
  42. 42.
    Tsai M, Takeishi T, Thompson H, et al. Induction of Mast Cell Proliferation, Maturation and Heparin Synthesis by the Rat C-Kit Lligand, Stem Cell Factor. Proc Natl Acad Sci USA 1991;88:6382–6386.PubMedCrossRefGoogle Scholar
  43. 43.
    Dastych J, Metcalfe DD. Stem Cell Factor Induces Mast Cell Adhesion to Fibronectin. J Immunol 1994;152:213–219.PubMedGoogle Scholar
  44. 44.
    Lukacs NW, Kunkel SL, Strieter RM, et al. The Role of Stem Cell Factor (C-Kit Ligand) and Inflammatory Cytokines in Pulmonary Mast Cell Activation. Blood 1996;87:2262–2268.PubMedGoogle Scholar
  45. 45.
    Rennick D, Hunte B, Holland G, et al. Cofactors are Essential for Stem Cell Factor- Dependent Growth and Maturation of Mast Cell Progenitors: Comparative Effects of Interleukin-3 (IL-3), IL-4, IL-10, and Fibroblasts. Blood 1995;85:57–65.PubMedGoogle Scholar
  46. 46.
    Frangogiannis NG, Mendoza LH, Lindsey ML, et al. IL-10 is Induced in the Reperfused Myocardium and May Modulate the Reaction to Injury. J Immunol 2000;165:2798–2808.PubMedGoogle Scholar
  47. 47.
    Pennington DW, Ruoss SJ, Gold WM. Dog Mastocytoma Cells Secrete a Growth Factor for Fibroblasts. Am J Respir Cell Mol Biol 1992;6:625–632.PubMedGoogle Scholar
  48. 48.
    de Almeida A, Mustin D, Forman MF, et al. Effects of Mast Cells on the Behavior of Isolated Heart Fibroblasts: Modulation of Collagen Remodeling and Gene Expression. J Cell Physiol 2002;191:51–59.PubMedCrossRefGoogle Scholar
  49. 49.
    Ruoss SJ, Hartmann T, Caughey GH. Mast Cell Tryptase is a Mitogen for Cultured Fibroblasts. J Clin Invest 1991;88:493–499.PubMedCrossRefGoogle Scholar
  50. 50.
    Cairns JA, Walls AF. Mast Cell Tryptase Stimulates the Synthesis of Type I Collagen in Human Lung Fibroblasts. J Clin Invest 1997;99:1313–1321.PubMedCrossRefGoogle Scholar
  51. 51.
    Gailit J, Marchese MJ, Kew RR, et al. The Differentiation and Function of Myofibroblasts is Regulated by Mast Cell Mediators. J Invest Dermatol 2001;117:1113–1119.PubMedCrossRefGoogle Scholar
  52. 52.
    Fang KC, Wolters PJ, Steinhoff M, et al. Mast Cell Expression of Gelatinases A and B is Regulated by Kit Ligand and TGF-beta. J Immunol 1999;162:5528–5535.PubMedGoogle Scholar
  53. 53.
    Chancey AL, Brower GL, Janicki JS. Cardiac Mast Cell-Mediated Activation of Gelatinase and Alteration of Ventricular Diastolic Function. Am J Physiol - Heart Circ Physiol 2002;282:H2152–H2158.PubMedGoogle Scholar
  54. 54.
    Ribatti D, Crivellato E, Candussio L, et al. Mast Cells and Their Secretory Granules are Angiogenic in the Chick Embryo Chorioallantoic Membrane. Clin Exp Allergy 2001;31:602–608.PubMedCrossRefGoogle Scholar
  55. 55.
    Blair RJ, Meng H, Marchese MJ, et al. Human Mast Cells Stimulate Vascular Tube Formation. Tryptase is a Novel, Potent Angiogenic Factor. J Clin Invest 1997;99:2691–2700.PubMedCrossRefGoogle Scholar
  56. 56.
    Ren G, Michael LH, Entman ML, et al. Morphological Characteristics of the Microvasculature in Healing Myocardial Infarcts. J Histochem Cytochem 2002;50:71–79.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Nikolaos G. Frangogiannis
    • 1
    • 2
  • Mark L. Entman
    • 1
    • 2
  1. 1.Section of Cardiovascular SciencesThe Methodist Hospital and The DeBakey Heart CenterHoustonUSA
  2. 2.Department of MedicineBaylor College of MedicineHoustonUSA

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