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Apoptosis of skeletal muscle cells and the pathogenesis of Myositis: A perspective

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Abstract

Apoptosis is a genetically controlled form of cell death that occurs in many biologic processes including embryogenesis, immune cell development, and maintenance of peripheral immune tolerance. Recent studies have yielded evidence suggesting that apoptosis of parenchymal cells may play a role in providing self-antigens to initiate autoimmune reactions. Skeletal muscle cells are fully differentiated and multinucleated. Apoptosis has been described in developing myoblasts and, recently, in mature myotubes. However, the involvement of apoptosis in skeletal muscle pathologies is unclear. This article reviews the available data concerning the occurrence of skeletal muscle cell apoptosis in selected muscle diseases. It also discusses the potential role of muscle cell apoptosis in the development of autoimmune diseases such as idiopathic inflammatory myopathies.

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References and Recommended Reading

  1. Duvall E, Wyllie AH: Death and the cell. Immunol Today 1986, 7:115–119.

    Article  CAS  Google Scholar 

  2. Nagata S: Apoptosis by death factor. Cell 1997, 88:355–365.

    Article  PubMed  CAS  Google Scholar 

  3. Cohen GM: Caspases: the executioners of apoptosis. Biochem J 1997, 326:1–16.

    PubMed  CAS  Google Scholar 

  4. Hengartner MO: The biochemistry of apoptosis. Nature 2000, 407:770–776.

    Article  PubMed  CAS  Google Scholar 

  5. Kromer G, Reed JC: Mitochondrial control of cell death. Nature Med 2000, 6:513–519.

    Article  CAS  Google Scholar 

  6. Fadok VA, Bratton DL, Frasch SC, Warner ML, Henson PM: The role of phosphatidylserine in recognition of apoptosis by phagocytes. Cell Death Differ 1998, 5:557–563.

    Article  CAS  Google Scholar 

  7. Savill J, Fadok V: Corpose clearance defines the meaning of cell death. Nature 2000, 407:784–788.

    Article  PubMed  CAS  Google Scholar 

  8. Kerr JFR, Wyllie AH, Currie AR: Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972, 26:239–257.

    PubMed  CAS  Google Scholar 

  9. Gavrieli Y, Sherman Y, Ben-Sasson SA: Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 1992, 119:493–501.

    Article  PubMed  CAS  Google Scholar 

  10. Wyllie AH: Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 1980, 284:555–556.

    Article  PubMed  CAS  Google Scholar 

  11. Lazebnik AY, Kaufmann SH, Desnoyers S, Poirier GG, Earnshaw WC: Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature 1994, 371:346–347.

    Article  PubMed  CAS  Google Scholar 

  12. Marzo I, Brenner C, Zamzami N, et al.: The permeability transition pore complex: a target for apoptosis regulation by caspases and bcl-2-related proteins. J Exp Med 1998, 187:1261–1271.

    Article  PubMed  CAS  Google Scholar 

  13. Sgnoc R, Gruber J: Apoptosis detection, an overview. Exp Gerontol 1998, 33:525–533.

    Article  Google Scholar 

  14. Saraste A: Morphologic criteria and detection of apoptosis. Herz 1999, 24:189–195.

    Article  PubMed  CAS  Google Scholar 

  15. Jacobson MD, Weil M, Raff C: Programmed cell death in animal development. Cell 1997, 88:347–354.

    Article  PubMed  CAS  Google Scholar 

  16. Cohen JJ, Duke RC, Fadok VA, Sellins KS: Apoptosis and programmed cell death in immunity. Annu Rev Immunol 1992, 10:267–293.

    Article  PubMed  CAS  Google Scholar 

  17. Rudin CM, Thompson CB: Apoptosis and disease: regulation and clinical relevance of programmed cell death. Annu Rev Med 1997, 48:267–281.

    Article  PubMed  CAS  Google Scholar 

  18. Suda T, Nagata S: Purification and characterization of the Fas-ligand that induces apoptosis. J Exp Med 1994, 179:873–879.

    Article  PubMed  CAS  Google Scholar 

  19. Liu C-C, Walsh CM, Young JD-E: Perforin: structure and function. Immunol Today 1995, 16:194–201.

    Article  PubMed  Google Scholar 

  20. Henkart PA: Lymphocyte-mediated cytotoxicity: two pathways and multiple effector molecules. Immunity 1994, 1:343–346.

    Article  PubMed  CAS  Google Scholar 

  21. Navratil JS, Ahearn JM: Apoptosis and autoimmunity: complement deficiency and systemic lupus erythematosus revisited. Curr Rheumatol Rep 2000, 2:32–38.

    PubMed  CAS  Google Scholar 

  22. Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S: Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediated apoptosis. Nature 1992, 356:314–317.

    Article  PubMed  CAS  Google Scholar 

  23. Takahashi T, Tanaka M, Brannan CI, et al.: Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell 1994, 76:969–976.

    Article  PubMed  CAS  Google Scholar 

  24. Drappa J, Vaishnaw AK, Sullivan KE, Chu JL, Elkon EB: Fas gene mutations in the Canale-Smith syndrome, an inherited lymphoproliferative disorder associated with autoimmunity. N Engl J Med 1996, 335:1643–1649.

    Article  PubMed  CAS  Google Scholar 

  25. Wang J, Zheng L, Lobito A, et al.: Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II. Cell 1999, 98:47–58.

    Article  PubMed  CAS  Google Scholar 

  26. Casciola-Rosen LA, Anhalt G, Rosen A: Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med 1994, 179:1317–1330.

    Article  PubMed  CAS  Google Scholar 

  27. Kerr JFR, Harmon B, Searle J: An electron-microscope study of cell deletion in the anuran tadpole tail during spontaneous metamorphosis with special reference to apoptosis of striated muscle fibers. J Cell Sci 1974, 14:571–585.

    PubMed  CAS  Google Scholar 

  28. Garcia-Martinez V, Macias D, Garian Y, et al.: Internucleosomal DNA fragmentation and programmed cell death (apoptosis) in the interdigital tissue of the embryonic chick leg bud. J Cell Sci 1993, 106:201–208.

    PubMed  CAS  Google Scholar 

  29. Fidzianska A: Apoptosis in human embryonic and diseased skeletal muscle. Basic Appl Myol 1996, 6:261–264.

    Google Scholar 

  30. Wang J, Walsh K: Resistance to apoptosis conferred by Cdk inhibitors during myocyte differentiation. Science 1996, 273:359–361.

    Article  PubMed  CAS  Google Scholar 

  31. Tews DS, Goebel HH: DNA fragmentation and expression of apoptosis-related proteins in muscular dystrophies. Neuropathol Appl Neurobiol 1997, 23:331–338.

    Article  PubMed  CAS  Google Scholar 

  32. Di Giovanni S, Mirabella M, D’Amico A, Tonali P, Servidei S: Apoptotic features accompany acute quadriplegic myopathy. Neurology 2000, 55:854–858.

    Google Scholar 

  33. Olive M, Martinez-Matos JA, Montero J, Ferrer I: Apoptosis is not the mechanism of cell death of muscle fibers in human muscular dystrophies and inflammatory myopathies. Muscle Nerve 1997, 20:1328–1330.

    Article  PubMed  CAS  Google Scholar 

  34. Sandri M, Carraro U: Apoptosis of skeletal muscle during development and disease. Int J Biochem Cell Biol 1999, 31:1373–1390.

    Article  PubMed  CAS  Google Scholar 

  35. Fidzianska A, Kaminska A: Apoptosis, a basic pathological reaction of injured neonatal muscle. Pediatr Pathol 1991, 11:421–429.

    PubMed  CAS  Google Scholar 

  36. Kaminska AM, Fidzianska A: Experimental induction of apoptosis and necrosis in neonatal rat skeletal muscle. Basic Appl Myol 1996, 6:251–256.

    Google Scholar 

  37. Behrens L, Bender A, Johnson MA, Hohlfeld R: Cytotoxic mechanisms in inflammatory myopathies: co-expression of Fas and protective Bcl-2 in muscle fibers and inflammatory cells. Brain 1997, 120:929–938.

    Article  PubMed  Google Scholar 

  38. Nagaraju K, Casciola-Rosen L, Rosen A, et al.: The inhibition of apoptosis in myositis and in normal muscle cells. J Immunol 2000, 164:459–465.

    Google Scholar 

  39. Koseki T, Inohara N, Chen S, Nunez G: ARC, an inhibitor of apoptosis expressed in skeletal muscle and heart that interacts selectively with caspases. Proc Natl Acad Sci USA 1998, 95:5156–5160.

    Article  PubMed  CAS  Google Scholar 

  40. Abu-Shakra S, Alhalabi MS, Nachtman FC, Schemidt RA, Brusilow WSA: Anabolic steroids induce injury and apoptosis of differentiated skeletal muscle. J Neurosci Res 1997, 47:186–197.

    Article  PubMed  CAS  Google Scholar 

  41. McArdle A, Maglara A, Appleton P, et al.: Apoptosis in multinucleated skeletal muscle myotubes. Lab Invest 1999, 79:1069–1076.

    PubMed  CAS  Google Scholar 

  42. Sandri M, Massimino ML, Cantini M, et al.: Dystrophin deficient myotubes undergo apoptosis in mouse primary muscle cell culture after DNA damage. Neurosci Lett 1998, 252:123–126.

    Article  PubMed  CAS  Google Scholar 

  43. Vachon PH, Loechel F, Xu H, Wewer UM, Engvall E: Merosin and laminin in myogenesis: specific requirement for merosin in myotube stability and survival. J Cell Biol 1996, 134:1483–1497.

    Article  PubMed  CAS  Google Scholar 

  44. Landing BH, Dixon LG, Wells TR: Studies on isolated human skeletal muscle fibers: including a proposed pattern of nuclear distribution and a concept of nuclear territories. Human Pathol 1974, 5:441–461.

    Article  CAS  Google Scholar 

  45. Cullen MJ, Mastaglia FL: Morphological changes in dystrophic muscle. Br Med Bull 1989, 36:145–152.

    Google Scholar 

  46. Hoffman E, Brown RH, Kunkel LM: Dystrophin, the protein product of the Duchenne muscular dystrophy locus. Cell 1987, 51:919–928.

    Article  PubMed  CAS  Google Scholar 

  47. Bulfield G, Siller WG, Wight PAL, Moore KJ: X-chromosome linked muscular dystrophy (mdx) in the mouse. Proc Natl Acad Sci USA 1984, 81:1189–1192.

    Article  PubMed  CAS  Google Scholar 

  48. Tidball JG, Albercht DE, Lokensgard BE, Spencer MJ: Apoptosis proceeds necrosis of dystrophin-deficient muscle. J Cell Sci 1995, 108:2197–2204.

    PubMed  CAS  Google Scholar 

  49. Sandri M, Podhorska-Okolow M, Geromel V, et al.: Exercise induces myonuclear ubiquitination and apoptosis in dystrophin-deficient muscle of mice. J Neuropathol Exp Neurol 1997, 56:45–57.

    PubMed  CAS  Google Scholar 

  50. Spencer MJ, Walsh CM, Dorshkind KA, Rodriguez EM, Tidball JG: Myonuclear apoptosis in dystrophic mdx muscle occurs by perforin-mediated cytotoxicity. J Clin Invest 1997, 99:2745–2751.

    PubMed  CAS  Google Scholar 

  51. Dalakas MC: Polymyositis, dermatomyositis, and inclusionbody myositis. N Engl J Med 1991, 325:1487–1498.

    Article  PubMed  CAS  Google Scholar 

  52. Sandri M, Minetti C, Pedemonte M, Carraro U: Apoptotic myonuclei in human Duchenne muscular dystrophy. Lab Invest 1998, 78:1005–1016.

    PubMed  CAS  Google Scholar 

  53. Migheli A, Mongini T, Doriguzzi C, et al.: Muscle apoptosis in humans occurs in normal and denervated muscle, but not in myotopic dystrophy, dystrophinopathies or inflammatory disease. Neurogenetics 1997, 1:81–87.

    Article  PubMed  CAS  Google Scholar 

  54. Hikida RS, Van Norstran S, Murray JD, et al.: Myonuclear loss in atrophied soleus muscle fibers. Anat Rec 1997, 247:350–354.

    Article  PubMed  CAS  Google Scholar 

  55. Allen D, Linderman J, Roy R, et al.: Apoptosis: a mechanism contributing to remodeling of skeletal muscle in response to hindlimb unweighting. Am J Physiol 1998, 273:C579-C587.

    Google Scholar 

  56. Tews D, Goebel HH, Schneider G, et al.: DNA fragmentation and expression of apoptosis-related proteins in experimentally denervated and reinnervated rat facial muscle. Neuropathol Appl Neurobiol 1997, 23:141–149.

    Article  PubMed  CAS  Google Scholar 

  57. Smith HK, Maxwell L, Martyn JA, Bass JJ: Nuclear DNA fragmentation and morphological alterations in adult rabbit skeletal muscle after short-term immobilization. Cell Tissue Res 2000, 302:235–241.

    Article  PubMed  CAS  Google Scholar 

  58. Fidzianska A, Goebel HH, Warlo I: Acute infantile spinal muscular atrophy muscle apoptosis as a proposed pathogenetic mechanism. Brain 1990, 113:265–273.

    Article  Google Scholar 

  59. Tews DS, Goebel HH: DNA fragmentation and Bcl-2 expression in infantile spinal muscular atrophy. Neuromuscul Disord 1996, 6:265–273.

    Article  PubMed  CAS  Google Scholar 

  60. Adams V, Jiang H, Yu S, et al.: Apoptosis in skeletal myocytes of patients with chronic heart failure is associated with exercise intolerance. J Am Coll Cardiol 1999, 33:956–965.

    Article  Google Scholar 

  61. Vescovo G, Zennaro R, Sandri M, et al.: Apoptosis of skeletal muscle myofibers and interstitial cells in experimental heart failure. J Mol Cell Cardiol 1998, 30:2449–2459.

    Article  PubMed  CAS  Google Scholar 

  62. Knight KR, Messina A, Hurley JV, et al.: Muscle cells become necrotic rather than apoptotic during reperfusion of ischaemic skeletal muscle. Int J Exp Pathol 1999, 80:169–175.

    Article  PubMed  CAS  Google Scholar 

  63. Iannone G, Cauli A, Yanni G, et al.: T-lymphocyte immunophenotyping in polymyositis and dermatomyositis. Br J Rheumatol 1996, 35:839–845.

    Article  PubMed  CAS  Google Scholar 

  64. Sugiura T, Murakawa Y, Nagai A, Kondo M, Kobayashi S: Fad and Fas ligand interaction induces apoptosis in inflammatory myopathies. Arthritis Rheum 1999, 42:291–298.

    Article  PubMed  CAS  Google Scholar 

  65. Utz PJ, Anderson P: Posttranslational protein modifications, apoptosis, and the bypass of tolerance to autoantigens. Arthritis Rheum 1998, 41:1152–1160.

    Article  PubMed  CAS  Google Scholar 

  66. Rosen A, Casciola-Rosen L: Autoantigens as substrates for apoptotic proteases: implications for the pathogenesis of systemic autoimmune disease. Cell Death Differ 1999, 6:6–12.

    Article  PubMed  CAS  Google Scholar 

  67. Hohlfeld R, Engel AG, Boebels N, Behrens L: Cellular immune mechanisms in inflammatory myopathies. Curr Opin Rheumatol 1999, 9:520–526.

    Article  Google Scholar 

  68. Targoff IN, Miller FW, Medsger TA Jr, Oddis CV: Classification criteria for the idiopathic inflammatory myopathies. Curr Opin Rheumatol 1997, 9:527–535.

    Article  PubMed  CAS  Google Scholar 

  69. Arnett FC, Tarfogg IF, Mimori T, et al.: Interrelationship of major histocompatibility complex class II alleles and autoantibodies in four ethnic groups with various forms of myositis. Arthritis Rheum 1996, 39:1507–1518.

    Article  PubMed  CAS  Google Scholar 

  70. Dalakas MC: Molecular immunology and genetics of inflammatory muscle diseases. Arch Neurol 1998, 55:1509–1512.

    Article  PubMed  CAS  Google Scholar 

  71. Goebels N, Michaells D, Engelhardt M, et al.: Differential expression of perforin in muscle-infiltrating T cells in polymyositis and dermatomyositis. J Clin Invest 1996, 97:2905–2910.

    Article  PubMed  CAS  Google Scholar 

  72. Cherin P, Herson S, Crevon MC, et al.: Mechanisms of lysis by activated cytotoxic cells expressing perforin and granzyme B genes and the protein TIA-1 in muscle biopsies of myositis. J Rheumatol 1996, 23:1135–1142.

    PubMed  CAS  Google Scholar 

  73. Bevan MJ: Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 cytotoxic cells which do not cross-react in the cytotoxicity assay. J Exp Med 1976, 143:1283–1288.

    Article  PubMed  CAS  Google Scholar 

  74. Kovacsovics-Bankowski M, Rock KL: A phagosome-to-cytosol pathway for exogenous antigens presented on MHC class I molecule. Science 1995, 267:243–246.

    Article  PubMed  CAS  Google Scholar 

  75. Banchereau J, Steinman RM: Dendritic cells and the control of immunity. Nature 1998, 392:245–252.

    Article  PubMed  CAS  Google Scholar 

  76. Albert ML, Sauter B, Bhardwaj N: Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 1998, 392:86–89. Dendritic cells exposed to apoptotic monocytes that were infected with influenza virus acquire antigens and can induce a virus-specific CTL response. This study demonstrates that apoptotic cells can be immunogenic.

    Article  PubMed  CAS  Google Scholar 

  77. Albert ML, Pearce SF, Francisco LM, et al.: Immature dendritic cells phagocytose apoptotic cells via alphaVbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med 1998, 188:1359–1368. This study demonstrates that immature, but not mature, dendritic cells phagocytose and process apoptotic cells, and present apoptotic cell-derived antigens to CTLs.

    Article  PubMed  CAS  Google Scholar 

  78. Rovere P, Sabbadini MG, Vallinoto C, et al.: Delayed clearance of apoptotic lymphoma cells allows cross-presentation of intracellular antigens by mature dendritic cells. J Leukocyte Biol 1999, 66:345–349.

    PubMed  CAS  Google Scholar 

  79. Shi L, Kam C-M, Powers JC, Aebersold R, Greenberg AH: Purification of three cytotoxic lymphocyte granule serine proteases that induce apoptosis through distinct substrate and target cell interaction. J Exp Med 1992, 176:1521–1529.

    Article  PubMed  CAS  Google Scholar 

  80. Shiver JW, Su L, Henkart PA: Cytotoxicity with target DNA breakdown by rat basophilic leukemia cells expressing both cytolysin and granzyme A. Cell 1992, 71:315–322.

    Article  PubMed  CAS  Google Scholar 

  81. Darmon AJ, Nicholson DW, Bleackley RC: Activation of the apoptotic protease CPP32 by cytotoxic T-cell-derived granzyme B. Nature 1995, 377:446–448.

    Article  PubMed  CAS  Google Scholar 

  82. Duan H, Orth K, Chinnaiyan AM, et al.: ICE-LAP6, a novel member of the ICE/Ced-3 gene family, is activated by the cytotoxic T cell protease granzyme B. J Biol Chem 1996, 271:16720–16724.

    Article  PubMed  CAS  Google Scholar 

  83. Talanian RV, Yang XH, Turbov J, et al.: Granule-mediated killing: pathways for granzyme B-initiated apoptosis. J Exp Med 1997, 186:1323–1331.

    Article  PubMed  CAS  Google Scholar 

  84. Casciola-Rosen L, Andrade F, Ulanet D, Wong WB, Rosen A: Cleavage by granzyme B is strongly predictive of autoantigen status: implications for initiation of autoimmunity. J Exp Med 1999, 20:815–825. This study demonstrates that a wide range of autoantigens targeted in systemic or organ-specific autoimmune diseases are cleaved by granzyme B in unique ways during CTL-induced apoptosis. These results suggest that CTL-mediated cell damage may produce cryptic epitopes on self-proteins that can potentially break immune tolerance to those proteins.

    Article  Google Scholar 

  85. Mathews MB, Bernstein RM: Myositis autoantibody inhibits histidyl-tRNA synthetase: a model for autoimmunity. Nature 1983, 304:177–179.

    Article  PubMed  CAS  Google Scholar 

  86. Nilasena DS, Trieu EP, Targoff IN: Analysis of the Mi-2 autoantigens in dermatomyositis. Arthritis Rheum 1995, 38:123–128.

    Article  PubMed  CAS  Google Scholar 

  87. Utz PJ, Hottelet M, Schur PH, Anderson P: Proteins phosphorylated during stress-induced apoptosis are common targets for autoantibody production in patients with systemic lupus erythematosus. J Exp Med 1997, 185:843–854. This study suggests that phosphorylation of self-proteins may render them immunogenic with the potential to break immune tolerance.

    Article  PubMed  CAS  Google Scholar 

  88. Bowles NE, Dubowitz V, Sewry CA, Archard LC: Dermatomyositis, polymyositis, and Coxsackie-B-virus infection. Lancet 1987, i:1004–1007.

    Article  Google Scholar 

  89. Aichele P, Bachmann MF, Hengartner H, Zinkernagel RM: Immunopathology or organ-specific autoimmunity as a consequence of virus infection. Immunol Rev 1996, 152:21–45.

    Article  PubMed  CAS  Google Scholar 

  90. Hinshaw VS, Olsen CW, Dybdahl-Sissoko N, Evans D: Apoptosis: a mechanism of cell killing by influenza A and B viruses. J Virol 1994, 68:3667–3673.

    PubMed  CAS  Google Scholar 

  91. Young LS, Dawson CW, Eliopoulos AG: Virus and apoptosis. Br Med Bull 1997, 53:509–521.

    PubMed  CAS  Google Scholar 

  92. Hogquist KA, Nett MA, Unanue ER, Chaplin DD: Interleukin 1 is processed and released during apoptosis. Proc Natl Acad Sci USA 1991, 88:8485–8489.

    Article  PubMed  CAS  Google Scholar 

  93. Knies UE, Behrensdorf HA, Mitchell CA, et al.: Regulation of endothelial monocyte-activating polypeptide II release by apoptosis. Proc Natl Acad Sci USA 1998, 95:12322–12327.

    Article  PubMed  CAS  Google Scholar 

  94. Wakasugi K, Schimmel P: Two distinct cytokines released from a human aminoacyl-tRNA synthetase. Science 1999, 284:147–150. This study shows that human tyrosyl tRNA-synthetase is released from apoptotic cells and is cleaved to become two fragments with chemokine activities. These results imply a role for apoptotic cells in inflammatory reactions.

    Article  PubMed  CAS  Google Scholar 

  95. Mathews MB, Reichin M, Hughes GRV, Bernstein RM: Antithreonyl-tRNA synthetase, a second myositis-related autoantibody. J Exp Med 1984, 160:420–434.

    Article  PubMed  CAS  Google Scholar 

  96. Hirakata M, Suwa A, Nagai S, et al.: Anti-KS: identification of autoantibodies to asparaginyl-transfer RNA synthetase associated with interstitial lung disease. J Immunol 1999, 162:2315–2320.

    PubMed  CAS  Google Scholar 

  97. Rosen A, Casciola-Rosen L, Ahearn J: Novel package of viral and self-antigens are generated during apoptosis. J Exp Med 1995, 181:1557–1561.

    Article  PubMed  CAS  Google Scholar 

  98. Botto M, Dell’Agnola C, Bygrave AE, et al.: Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nature Genet 1998, 19:56–61. This study demonstrates that apoptotic bodies accumulate in the glomeruli of C1q-knockout mice and these mice develop glomerulonephritis. These data suggest that C1q is involved in the recognition and clearance of apoptotic cells in vivo.

    Article  PubMed  CAS  Google Scholar 

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Liu, CC., Ahearn, J.M. Apoptosis of skeletal muscle cells and the pathogenesis of Myositis: A perspective. Curr Rheumatol Rep 3, 325–333 (2001). https://doi.org/10.1007/s11926-001-0037-y

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