Advertisement

Complement System Activation in Cardiac and Skeletal Muscle Pathology: Friend or Foe?

  • Maro Syriga
  • Manolis MavroidisEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 735)

Abstract

A major goal in current cardiology practice is to determine optimal strategies for minimizing myocardial necrosis and optimizing cardiac repair following an acute myocardial infarction. Temporally regulated activation and suppression of innate immunity may be critical for achieving this goal. Extensive experimental data in various animal models have indicated that inhibiting complement activation offers protection to cardiac tissue after ischemia/reperfusion. However, the results of clinical studies using complement inhibitors (mainly at the C5 level) in patients with acute myocardial infarction have largely been disappointing.

In cases in which complement activation participates in the initial events of muscle cell destruction, as in autoimmune myocarditis or autoimmune muscle disorders, inhibition of complement activation is expected to prove a successful treatment. In other pathologic conditions in which complement is recruited by degenerating or dying muscle cells, as in ischemia, the ideal approach is probably to modulate rather than abruptly blunt complement activation. Beneficial effects of complement action with regard to waste disposal, recruitment of stem cells, regeneration, angiogenesis, and better utilization of energy sources under hypoxic conditions may also prove important for successful disease treatment. Patient outcome after myocardial infarction almost certainly depend upon the combined activation of several distinct but potentially interrelated signaling pathways, suggesting that a combination of treatments targeted to different pathways should be the therapy of choice, and modulation of complement could be one of them.

Keywords

Complement Activation Inclusion Body Myositis Inflammatory Myopathy Membrane Attack Complex Complement Cascade 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Abbott JD, Huang Y et al (2004) Stromal cell-derived factor-1alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation 110(21):3300–3305CrossRefGoogle Scholar
  2. Askari AT, Unzek S et al (2003) Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet 362(9385):697–703CrossRefPubMedPubMedCentralGoogle Scholar
  3. Basta M, Dalakas MC (1994) High-dose intravenous immunoglobulin exerts its beneficial effect in patients with dermatomyositis by blocking endomysial deposition of activated complement fragments. J Clin Invest 94(5): 1729–1735CrossRefPubMedPubMedCentralGoogle Scholar
  4. Cenacchi G, Fanin M et al (2005) Ultrastructural changes in dysferlinopathy support defective membrane repair mechanism. J Clin Pathol 58(2):190–195CrossRefPubMedPubMedCentralGoogle Scholar
  5. Chamberlain-Banoub J, Neal JW et al (2006) Complement membrane attack is required for endplate damage and ­clinical disease in passive experimental myasthenia gravis in Lewis rats. Clin Exp Immunol 146(2):278–286CrossRefPubMedPubMedCentralGoogle Scholar
  6. Chen XL, Tummala PE et al (1998) Angiotensin II induces monocyte chemoattractant protein-1 gene expression in rat vascular smooth muscle cells. Circ Res 83(9):952–959CrossRefGoogle Scholar
  7. Choi YH, Kurtz A et al (2011) Mesenchymal stem cells for cardiac cell therapy. Hum Gene Ther 22(1):3–17CrossRefGoogle Scholar
  8. Collins RA, Grounds MD (2001) The role of tumor necrosis factor-alpha (TNF-alpha) in skeletal muscle regeneration. Studies in TNF-alpha(−/−) and TNF-alpha(−/−)/LT-alpha(−/−) mice. J Histochem Cytochem 49(8):989–1001CrossRefGoogle Scholar
  9. Corti S, Salani S et al (2001) Chemotactic factors enhance myogenic cell migration across an endothelial monolayer. Exp Cell Res 268(1):36–44CrossRefGoogle Scholar
  10. Crawford MH, Grover FL et al (1988) Complement and neutrophil activation in the pathogenesis of ischemic myocardial injury. Circulation 78(6):1449–1458CrossRefGoogle Scholar
  11. Dalakas MC (2010a) Immunotherapy of myositis: issues, concerns and future prospects. Nat Rev Rheumatol 6(3):129–137CrossRefGoogle Scholar
  12. Dalakas MC (2010b) Inflammatory muscle diseases: a critical review on pathogenesis and therapies. Curr Opin Pharmacol 10(3):346–352CrossRefGoogle Scholar
  13. Diepenhorst GM, van Gulik TM et al (2009) Complement-mediated ischemia-reperfusion injury: lessons learned from animal and clinical studies. Ann Surg 249(6):889–899CrossRefGoogle Scholar
  14. Emslie-Smith AM, Engel AG (1990) Microvascular changes in early and advanced dermatomyositis: a quantitative study. Ann Neurol 27(4):343–356CrossRefPubMedPubMedCentralGoogle Scholar
  15. Engler R (1987) Consequences of activation and adenosine-mediated inhibition of granulocytes during myocardial ischemia. Fed Proc 46(7):2407–2412PubMedGoogle Scholar
  16. Eriksson U, Kurrer MO et al (2003) Interleukin-6-deficient mice resist development of autoimmune myocarditis associated with impaired upregulation of complement C3. Circulation 107(2):320–325CrossRefGoogle Scholar
  17. Faraj M, Cianflone K (2004) Differential regulation of fatty acid trapping in mouse adipose tissue and muscle by ASP. Am J Physiol Endocrinol Metab 287(1):E150–E159CrossRefGoogle Scholar
  18. Frangogiannis NG (2008) The immune system and cardiac repair. Pharmacol Res 58(2):88–111CrossRefPubMedPubMedCentralGoogle Scholar
  19. Gallardo E, Rojas-Garcia R et al (2001) Inflammation in dysferlin myopathy: immunohistochemical characterization of 13 patients. Neurology 57(11):2136–2138CrossRefGoogle Scholar
  20. Gasque P, Morgan BP et al (1996) Human skeletal myoblasts spontaneously activate allogeneic complement but are resistant to killing. J Immunol 156(9):3402–3411PubMedGoogle Scholar
  21. Han R, Frett EM et al (2010) Genetic ablation of complement C3 attenuates muscle pathology in dysferlin-deficient mice. J Clin Invest 120(12):4366–4374CrossRefPubMedPubMedCentralGoogle Scholar
  22. He S, Atkinson C et al (2009) A complement-dependent balance between hepatic ischemia/reperfusion injury and liver regeneration in mice. J Clin Invest 119(8):2304–2316PubMedPubMedCentralGoogle Scholar
  23. Hill JH, Ward PA (1971) The phlogistic role of C3 leukotactic fragments in myocardial infarcts of rats. J Exp Med 133(4):885–900CrossRefPubMedPubMedCentralGoogle Scholar
  24. Hirahashi J, Mekala D et al (2006) Mac-1 signaling via Src-family and Syk kinases results in elastase-dependent thrombohemorrhagic vasculopathy. Immunity 25(2):271–283CrossRefPubMedPubMedCentralGoogle Scholar
  25. Hori M, Nishida K (2009) Oxidative stress and left ventricular remodelling after myocardial infarction. Cardiovasc Res 81(3):457–464CrossRefGoogle Scholar
  26. Jain A, Sharma MC et al (2011) Detection of the membrane attack complex as a diagnostic tool in dermatomyositis. Acta Neurol Scand 123(2):122–129CrossRefGoogle Scholar
  27. Jennings RB, Murry CE et al (1990) Development of cell injury in sustained acute ischemia. Circulation 82(3 Suppl):II2–II12PubMedGoogle Scholar
  28. Jennings RB, Steenbergen C Jr et al (1995) Myocardial ischemia and reperfusion. Monogr Pathol 37:47–80PubMedGoogle Scholar
  29. Jiang B, Liao R (2010) The paradoxical role of inflammation in cardiac repair and regeneration. J Cardiovasc Transl Res 3(4):410–416CrossRefGoogle Scholar
  30. Kaya Z, Afanasyeva M et al (2001) Contribution of the innate immune system to autoimmune myocarditis: a role for complement. Nat Immunol 2(8):739–745CrossRefGoogle Scholar
  31. Kilgore KS, Homeister JW et al (1994) Sulfhydryl compounds, captopril, and MPG inhibit complement-mediated myocardial injury. Am J Physiol 266(1 Pt 2):H28–H35PubMedGoogle Scholar
  32. Kimura Y, Madhavan M et al (2003) Expression of complement 3 and complement 5 in newt limb and lens regeneration. J Immunol 170(5):2331–2339CrossRefGoogle Scholar
  33. Kissel JT, Mendell JR et al (1986) Microvascular deposition of complement membrane attack complex in dermatomyositis. N Engl J Med 314(6):329–334CrossRefGoogle Scholar
  34. Law SK, Gagnon J et al (1987) The primary structure of the beta-subunit of the cell surface adhesion glycoproteins LFA-1, CR3 and p150,95 and its relationship to the fibronectin receptor. EMBO J 6(4):915–919CrossRefPubMedPubMedCentralGoogle Scholar
  35. Legoedec J, Gasque P et al (1995) Expression of the complement alternative pathway by human myoblasts in vitro: biosynthesis of C3, factor B, factor H and factor I. Eur J Immunol 25(12):3460–3466CrossRefGoogle Scholar
  36. Legoedec J, Gasque P et al (1997) Complement classical pathway expression by human skeletal myoblasts in vitro. Mol Immunol 34(10):735–741CrossRefGoogle Scholar
  37. Leivo I, Engvall E (1986) C3d fragment of complement interacts with laminin and binds to basement membranes of glomerulus and trophoblast. J Cell Biol 103(3):1091–1100CrossRefGoogle Scholar
  38. Lennon VA, Seybold ME et al (1978) Role of complement in the pathogenesis of experimental autoimmune myasthenia gravis. J Exp Med 147(4):973–983CrossRefGoogle Scholar
  39. Lennon NJ, Kho A et al (2003) Dysferlin interacts with annexins A1 and A2 and mediates sarcolemmal wound-healing. J Biol Chem 278(50):50466–50473CrossRefGoogle Scholar
  40. Li X, Moody MR et al (2000) Cardiac-specific overexpression of tumor necrosis factor-alpha causes oxidative stress and contractile dysfunction in mouse diaphragm. Circulation 102(14):1690–1696CrossRefGoogle Scholar
  41. Liu J, Aoki M et al (1998) Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy. Nat Genet 20(1):31–36CrossRefGoogle Scholar
  42. Lloyd-Jones D, Adams R et al (2009) Heart disease and stroke statistics–2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 119(3):480–486CrossRefPubMedPubMedCentralGoogle Scholar
  43. Long KK, Pavlath GK et al (2011) Sca-1 influences the innate immune response during skeletal muscle regeneration. Am J Physiol Cell Physiol 300(2):C287–C294CrossRefGoogle Scholar
  44. MacLaren R, Cui W et al (2008) Adipokines and the immune system: an adipocentric view. Adv Exp Med Biol 632:1–21CrossRefGoogle Scholar
  45. Markiewski MM, Mastellos D et al (2004) C3a and C3b activation products of the third component of complement (C3) are critical for normal liver recovery after toxic injury. J Immunol 173(2):747–754CrossRefGoogle Scholar
  46. Markiewski MM, DeAngelis RA et al (2009) The regulation of liver cell survival by complement. J Immunol 182(9):5412–5418CrossRefPubMedPubMedCentralGoogle Scholar
  47. Mavroidis M, Capetanaki Y (2002) Extensive induction of important mediators of fibrosis and dystrophic calcification in desmin-deficient cardiomyopathy. Am J Pathol 160(3):943–952CrossRefPubMedPubMedCentralGoogle Scholar
  48. Mevorach D, Mascarenhas JO et al (1998) Complement-dependent clearance of apoptotic cells by human macrophages. J Exp Med 188(12):2313–2320CrossRefPubMedPubMedCentralGoogle Scholar
  49. Neely JR, Morgan HE (1974) Relationship between carbohydrate and lipid metabolism and the energy balance of heart muscle. Annu Rev Physiol 36:413–459CrossRefGoogle Scholar
  50. Nguyen HX, Tidball JG (2003) Interactions between neutrophils and macrophages promote macrophage killing of rat muscle cells in vitro. J Physiol 547(Pt 1):125–132CrossRefGoogle Scholar
  51. Nozaki M, Raisler BJ et al (2006) Drusen complement components C3a and C5a promote choroidal neovascularization. Proc Natl Acad Sci USA 103(7):2328–2333CrossRefGoogle Scholar
  52. Oksjoki R, Kovanen PT et al (2007) Function and regulation of the complement system in cardiovascular diseases. Front Biosci 12:4696–4708CrossRefGoogle Scholar
  53. Oram JF, Bennetch SL et al (1973) Regulation of fatty acid utilization in isolated perfused rat hearts. J Biol Chem 248(15):5299–5309PubMedGoogle Scholar
  54. Psarras S, Mavroidis M et al (2011) Regulation of adverse remodelling by osteopontin in a genetic heart failure model. Eur Heart J [Epub ahead of print]. doi:10.1093/eurheart/ehr119Google Scholar
  55. Qi H, Tuzun E et al (2008) C5a is not involved in experimental autoimmune myasthenia gravis pathogenesis. J Neuroimmunol 196(1–2):101–106CrossRefPubMedPubMedCentralGoogle Scholar
  56. Rajabi M, Kassiotis C et al (2007) Return to the fetal gene program protects the stressed heart: a strong hypothesis. Heart Fail Rev 12(3–4):331–343CrossRefGoogle Scholar
  57. Ratajczak MZ, Reca R et al (2006) Modulation of the SDF-1-CXCR4 axis by the third complement component (C3) – implications for trafficking of CXCR4+ stem cells. Exp Hematol 34(8):986–995CrossRefGoogle Scholar
  58. Rawat R, Cohen TV et al (2010) Inflammasome up-regulation and activation in dysferlin-deficient skeletal muscle. Am J Pathol 176(6):2891–2900CrossRefPubMedPubMedCentralGoogle Scholar
  59. Rezkalla SH, Kloner RA (2002) No-reflow phenomenon. Circulation 105(5):656–662CrossRefGoogle Scholar
  60. Sahashi K, Engel AG et al (1980) Ultrastructural localization of the terminal and lytic ninth complement component (C9) at the motor end-plate in myasthenia gravis. J Neuropathol Exp Neurol 39(2):160–172CrossRefGoogle Scholar
  61. Saraste A, Pulkki K et al (1997) Apoptosis in human acute myocardial infarction. Circulation 95(2):320–323CrossRefGoogle Scholar
  62. Schulz R, Heusch G (2009) Tumor necrosis factor-alpha and its receptors 1 and 2: Yin and Yang in myocardial infarction? Circulation 119(10):1355–1357CrossRefGoogle Scholar
  63. Soltys J, Kusner LL et al (2009) Novel complement inhibitor limits severity of experimentally myasthenia gravis. Ann Neurol 65(1):67–75CrossRefPubMedPubMedCentralGoogle Scholar
  64. Spitzer D, Unsinger J et al (2004) ScFv-mediated in vivo targeting of DAF to erythrocytes inhibits lysis by complement. Mol Immunol 40(13):911–919CrossRefGoogle Scholar
  65. Spuler S, Engel AG (1998) Unexpected sarcolemmal complement membrane attack complex deposits on nonnecrotic muscle fibers in muscular dystrophies. Neurology 50(1):41–46CrossRefGoogle Scholar
  66. Suzuki N, Aoki M et al (2005) Expression profiling with progression of dystrophic change in dysferlin-deficient mice (SJL). Neurosci Res 52(1):47–60CrossRefGoogle Scholar
  67. Tang Z, McGowan BS et al (2004) Gene expression profiling during the transition to failure in TNF-alpha over-expressing mice demonstrates the development of autoimmune myocarditis. J Mol Cell Cardiol 36(4):515–530CrossRefGoogle Scholar
  68. Tidball JG (2005) Inflammatory processes in muscle injury and repair. Am J Physiol Regul Integr Comp Physiol 288(2):R345–R353CrossRefGoogle Scholar
  69. Tidball JG, Villalta SA (2010) Regulatory interactions between muscle and the immune system during muscle regeneration. Am J Physiol Regul Integr Comp Physiol 298(5):R1173–R1187CrossRefPubMedPubMedCentralGoogle Scholar
  70. Tidball JG, Wehling-Henricks M (2007) Macrophages promote muscle membrane repair and muscle fibre growth and regeneration during modified muscle loading in mice in vivo. J Physiol 578(Pt 1):327–336CrossRefGoogle Scholar
  71. Tsonis PA, Del Rio-Tsonis K et al (1996) Can insights into urodele limb regeneration be achieved with cell cultures and retroviruses? Int J Dev Biol 40(4):813–816PubMedGoogle Scholar
  72. Tuzun E, Scott BG et al (2003) Genetic evidence for involvement of classical complement pathway in induction of experimental autoimmune myasthenia gravis. J Immunol 171(7):3847–3854CrossRefGoogle Scholar
  73. Tuzun E, Scott BG et al (2004) Circulating immune complexes augment severity of antibody-mediated myasthenia gravis in hypogammaglobulinemic RIIIS/J mice. J Immunol 172(9):5743–5752CrossRefGoogle Scholar
  74. Tuzun E, Li J et al (2007) Pros and cons of treating murine myasthenia gravis with anti-C1q antibody. J Neuroimmunol 182(1–2):167–176CrossRefGoogle Scholar
  75. Vandervelde S, van Luyn MJ et al (2005) Signaling factors in stem cell-mediated repair of infarcted myocardium. J Mol Cell Cardiol 39(2):363–376CrossRefGoogle Scholar
  76. Venkatachalam K, Venkatesan B et al (2009) WISP1, a pro-mitogenic, pro-survival factor, mediates tumor necrosis factor-alpha (TNF-alpha)-stimulated cardiac fibroblast proliferation but inhibits TNF-alpha-induced cardiomyocyte death. J Biol Chem 284(21):14414–14427CrossRefPubMedPubMedCentralGoogle Scholar
  77. Villalta SA, Nguyen HX et al (2009) Shifts in macrophage phenotypes and macrophage competition for arginine metabolism affect the severity of muscle pathology in muscular dystrophy. Hum Mol Genet 18(3):482–496CrossRefGoogle Scholar
  78. Vincent A, Drachman DB (2002) Myasthenia gravis. Adv Neurol 88:159–188PubMedGoogle Scholar
  79. Wenzel K, Zabojszcza J et al (2005) Increased susceptibility to complement attack due to down-regulation of decay-accelerating factor/CD55 in dysferlin-deficient muscular dystrophy. J Immunol 175(9):6219–6225CrossRefGoogle Scholar
  80. Yasojima K, Kilgore KS et al (1998) Complement gene expression by rabbit heart: upregulation by ischemia and ­reperfusion. Circ Res 82(11):1224–1230CrossRefGoogle Scholar
  81. Zhou Y, Gong B et al (2007) Anti-C5 antibody treatment ameliorates weakness in experimentally acquired myasthenia gravis. J Immunol 179(12):8562–8567CrossRefGoogle Scholar
  82. Zwaka TP, Manolov D et al (2002) Complement and dilated cardiomyopathy: a role of sublytic terminal complement complex-induced tumor necrosis factor-alpha synthesis in cardiac myocytes. Am J Pathol 161(2):449–457CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Center of Basic Research, Biomedical Research FoundationAcademy of AthensAthensGreece

Personalised recommendations