Skip to main content

Advertisement

Log in

Effects of functionally diverse calpain system on immune cells

  • Review
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Calpains are a family of nonlysosomal cysteine proteases, which play important roles in numerous physiological and pathological processes. Locations of them dictates the functions so that they are classified as ubiquitously expressed calpains and tissue-specific calpains. Recent studies are mainly focused on conventional calpains (calpain-1,2) in development and diseases, and increasing people pay attention to other subtypes of calpains but may not been summarized appropriately. Growing evidence suggests that calpains are also involved in immune regulation. However, seldom articles review the regulation of calpains on immune cells. The aim of this article is to review the research progress of each calpain isozyme and the effect of calpains on immune cells, especially the promotion effect of calpains on the immune response of macrophage, neutrophils, dendritic cells, mast cells, natural killed cells, and lymphocytes. These effects would hold great promise for the clinical application of calpains as a practicable therapeutic option in the treatment of immune related diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Araujo H, Julio A, Cardoso M. Translating genetic, biochemical and structural information to the calpain view of development. Mech Dev. 2018;154:240–50.

    Article  PubMed  CAS  Google Scholar 

  2. Tamtaji OR, Mirhosseini N, Reiter RJ, Azami A, Asemi Z. Melatonin, a calpain inhibitor in the central nervous system: current status and future perspectives. J Cell Physiol. 2019;234(2):1001–7.

    Article  PubMed  CAS  Google Scholar 

  3. Mahaman YAR, Huang F, Kessete Afewerky H, Maibouge TMS, Ghose B, Wang X. Involvement of calpain in the neuropathogenesis of Alzheimer's disease. Med Res Rev. 2019;39(2):608–30.

    Article  PubMed  Google Scholar 

  4. Nevzorova TA, Mordakhanova ER, Daminova AG, Ponomareva AA, Andrianova IA, Le Minh G, et al. Platelet factor 4-containing immune complexes induce platelet activation followed by calpain-dependent platelet death. Cell Death Discov. 2019;5:106.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Miyazaki T, Akasu R, Miyazaki A. Calpain proteolytic systems counteract endothelial cell adaptation to inflammatory environments. Inflamm Regen. 2020;40:5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Ding ZJ, Chen X, Tang XX, Wang X, Song YL, Chen XD, et al. Apoptosis-inducing factor and calpain upregulation in glutamate-induced injury of rat spiral ganglion neurons. Mol Med Rep. 2015;12(2):1685–92.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Dimeloe S, Burgener AV, Grahlert J, Hess C. T-cell metabolism governing activation, proliferation and differentiation; a modular view. Immunology. 2017;150(1):35–44.

    Article  PubMed  CAS  Google Scholar 

  8. Liu H, Chen R, Kang F, Lai H, Wang Y. KCNQ1OT1 promotes ovarian cancer progression via modulating MIR-142-5p/CAPN10 axis. Mol Genet Genomic Med. 2020;8(2):e1077.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Wang T, Gao Y, Wang X, Shi Y, Xu J, Wu B, et al. Calpain-10 drives podocyte apoptosis and renal injury in diabetic nephropathy. Diabetes Metab Syndr Obes. 2019;12:1811–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Wert KJ, Skeie JM, Bassuk AG, Olivier AK, Tsang SH, Mahajan VB. Functional validation of a human CAPN5 exome variant by lentiviral transduction into mouse retina. Hum Mol Genet. 2014;23(10):2665–77.

    Article  PubMed  CAS  Google Scholar 

  11. Richard I, Broux O, Allamand V, Fougerousse F, Chiannilkulchai N, Bourg N, et al. Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A. Cell. 1995;81(1):27–40.

    Article  PubMed  CAS  Google Scholar 

  12. Meng Y, Sun T, Wu C, Dong C, Xiong S. Calpain regulates CVB3 induced viral myocarditis by promoting autophagic flux upon infection. Microbes Infect. 2020;22(1):46–54.

    Article  PubMed  CAS  Google Scholar 

  13. Ono Y, Sorimachi H. Calpains: an elaborate proteolytic system. Biochim Biophys Acta. 2012;1824(1):224–36.

    Article  PubMed  CAS  Google Scholar 

  14. Kim D, Beckett J, Nagpal V, Seman-Senderos M, Gould R, Creamer T, et al. Calpain 9 as a therapeutic target in TGFβ-induced mesenchymal transition and fibrosis. Sci Transl Med. 2019;11(501):eaau2814.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Momeni HR. Role of calpain in apoptosis. Cell J. 2011;13(2):65–72.

    PubMed  PubMed Central  CAS  Google Scholar 

  16. Hosseini M, Najmabadi H, Kahrizi K. Calpains: diverse functions but enigmatic. Arch Iran Med. 2018;21(4):170–9.

    PubMed  Google Scholar 

  17. Sorimachi H, Mamitsuka H, Ono Y. Understanding the substrate specificity of conventional calpains. Biol Chem. 2012;393(9):853–71.

    Article  PubMed  CAS  Google Scholar 

  18. Wang Y, Bi X, Baudry M. Calpain-2 as a therapeutic target for acute neuronal injury. Expert Opin Ther Targets. 2018;22(1):19–29.

    Article  PubMed  CAS  Google Scholar 

  19. Nie Q, Zhu L, Zhang L, Leng B, Wang H. Astragaloside IV protects against hyperglycemia-induced vascular endothelial dysfunction by inhibiting oxidative stress and Calpain-1 activation. Life Sci. 2019;232:116662.

    Article  PubMed  CAS  Google Scholar 

  20. Siuda D, Randriamboavonjy V, Fleming I. Regulation of calpain 2 expression by miR-223 and miR-145. Biochim Biophys Acta Gene Regul Mech. 2019;1862(10):194438.

    Article  PubMed  CAS  Google Scholar 

  21. Bruening J, Lasswitz L, Banse P, Kahl S, Marinach C, Vondran FW, et al. Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB. PLoS Pathog. 2018;14(7):e1007111.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Schaefer KA, Toral MA, Velez G, Cox AJ, Baker SA, Borcherding NC, et al. Calpain-5 expression in the retina localizes to photoreceptor synapses. Invest Ophthalmol Vis Sci. 2016;57(6):2509–21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Coomer CE, Morris AC. Capn5 expression in the healthy and regenerating Zebrafish retina. Invest Ophthalmol Vis Sci. 2018;59(8):3643–54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Yan Q, Huang C, Jiang Y, Shan H, Jiang R, Wang J, et al. Calpain7 impairs embryo implantation by downregulating beta3-integrin expression via degradation of HOXA10. Cell Death Dis. 2018;9(3):291.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Li Z, Wang S, Huo X, Yu H, Lu J, Zhang S, et al. Cystatin C expression is promoted by VEGFA blocking, with inhibitory effects on endothelial cell Angiogenic functions including proliferation, migration, and Chorioallantoic membrane angiogenesis. J Am Heart Assoc. 2018;7(21):e009167.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Mo HY, Choi EJ, Yoo NJ, Lee SH. Inactivating mutations of tumor suppressor genes ABCA1 and CAPN13 in colorectal cancers. Pathol Res Pract. 2020;216(5):152870.

    Article  PubMed  CAS  Google Scholar 

  27. Hastings MH, Qiu A, Zha C, Farah CA, Mahdid Y, Ferguson L, et al. The zinc fingers of the small optic lobes calpain bind polyubiquitin. J Neurochem. 2018;146(4):429–45.

    Article  PubMed  CAS  Google Scholar 

  28. Kramerova I, Torres JA, Eskin A, Nelson SF, Spencer MJ. Calpain 3 and CaMKIIbeta signaling are required to induce HSP70 necessary for adaptive muscle growth after atrophy. Hum Mol Genet. 2018;27(9):1642–53.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Ono Y, Ojima K, Shinkai-Ouchi F, Hata S, Sorimachi H. An eccentric calpain, CAPN3/p94/calpain-3. Biochimie. 2016;122:169–87.

    Article  PubMed  CAS  Google Scholar 

  30. Miyazaki T, Miyazaki A. Emerging roles of calpain proteolytic systems in macrophage cholesterol handling. Cell Mol Life Sci. 2017;74(16):3011–21.

    Article  PubMed  CAS  Google Scholar 

  31. Ben-Aharon I, Brown P, Shalgi R, Eddy E. Calpain 11 is unique to mouse spermatogenic cells. Mol Reprod Dev. 2006;73(6):767–73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Bochner R, Samuelov L, Sarig O, Li Q, Adase CA, Isakov O, et al. Calpain 12 function revealed through the study of an atypical case of autosomal recessive congenital Ichthyosis. J Invest Dermatol. 2017;137(2):385–93.

    Article  PubMed  CAS  Google Scholar 

  33. V.A. Litosh, M. Rochman, J.K. Rymer, A. Porollo, L.C. Kottyan, M.E. Rothenberg, Calpain-14 and its association with eosinophilic esophagitis, J Allergy Clin Immunol, 139 (6) (2017) 1762–1771 e1767.

  34. Guan Y, Huang D, Chen F, Gao C, Tao T, Shi H, et al. Phosphorylation of Def regulates Nucleolar p53 turnover and cell cycle progression through Def recruitment of Calpain3. PLoS Biol. 2016;14(9):e1002555.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Hood JL, Logan BB, Sinai AP, Brooks WH, Roszman TL. Association of the calpain/calpastatin network with subcellular organelles. Biochem Biophys Res Commun. 2003;310(4):1200–12.

    Article  PubMed  CAS  Google Scholar 

  36. Ozaki T, Tomita H, Tamai M, Ishiguro S. Characteristics of mitochondrial calpains. J Biochem. 2007;142(3):365–76.

    Article  PubMed  CAS  Google Scholar 

  37. Arrington DD, Van Vleet TR, Schnellmann RG. Calpain 10: a mitochondrial calpain and its role in calcium-induced mitochondrial dysfunction. Am J Physiol Cell Physiol. 2006;291(6):C1159–71.

    Article  PubMed  CAS  Google Scholar 

  38. Arias A, Lucendo AJ. Molecular basis and cellular mechanisms of eosinophilic esophagitis for the clinical practice. Expert Rev Gastroenterol Hepatol. 2019;13(2):99–117.

    Article  PubMed  CAS  Google Scholar 

  39. Baudry M. Calpain-1 and Calpain-2 in the brain: Dr. Jekill and Mr Hyde? Curr Neuropharmacol. 2019;17(9):823–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Maki M. Structures and functions of penta-EF-hand calcium-binding proteins and their interacting partners: enigmatic relationships between ALG-2 and calpain-7. Biosci Biotechnol Biochem. 2020;84(4):651–60.

    Article  PubMed  CAS  Google Scholar 

  41. Brown AE, Yeaman SJ, Walker M. Targeted suppression of calpain-10 expression impairs insulin-stimulated glucose uptake in cultured primary human skeletal muscle cells. Mol Genet Metab. 2007;91(4):318–24.

    Article  PubMed  CAS  Google Scholar 

  42. Hong JM, Teitelbaum SL, Kim TH, Ross FP, Kim SY, Kim HJ. Calpain-6, a target molecule of glucocorticoids, regulates osteoclastic bone resorption via cytoskeletal organization and microtubule acetylation. J Bone Miner Res. 2011;26(3):657–65.

    Article  PubMed  CAS  Google Scholar 

  43. Hata S, Abe M, Suzuki H, Kitamura F, Toyama-Sorimachi N, Abe K, et al. Calpain 8/nCL-2 and calpain 9/nCL-4 constitute an active protease complex, G-calpain, involved in gastric mucosal defense. PLoS Genet. 2010;6(7):e1001040.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Davis J, Martin S, Patel P, Green A, Rakha E, Ellis I, et al. Low calpain-9 is associated with adverse disease-specific survival following endocrine therapy in breast cancer. BMC Cancer. 2014;14:995.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Chang YS, Hsu MJ, Chou RR. Postmortem role of calpain-11 in ostrich skeletal muscle. Meat Sci. 2018;143:147–52.

    Article  PubMed  CAS  Google Scholar 

  46. Kumar V, Ahmad A. Targeting calpains: a novel immunomodulatory approach for microbial infections. Eur J Pharmacol. 2017;814:28–44.

    Article  PubMed  CAS  Google Scholar 

  47. Schaecher K, Goust J, Banik N. The effects of calpain inhibition on IkB alpha degradation after activation of PBMCs: identification of the calpain cleavage sites. Neurochem Res. 2004;29(7):1443–51.

    Article  PubMed  CAS  Google Scholar 

  48. Sasahara Y. WASP-WIP complex in the molecular pathogenesis of Wiskott-Aldrich syndrome. Pediatr Int. 2016;58(1):4–7.

    Article  PubMed  CAS  Google Scholar 

  49. Penna D, Muller S, Martinon F, Demotz S, Iwashima M, Valitutti S. Degradation of ZAP-70 following antigenic stimulation in human T lymphocytes: role of calpain proteolytic pathway. J Immunol. 1999;163(1):50–6.

    Article  PubMed  CAS  Google Scholar 

  50. Liu CSC, Raychaudhuri D, Paul B, Chakrabarty Y, Ghosh AR, Rahaman O, et al. Cutting edge: Piezo1 Mechanosensors optimize human T cell activation. J Immunol. 2018;200(4):1255–60.

    Article  PubMed  CAS  Google Scholar 

  51. Rock MT, Dix AR, Brooks WH, Roszman TL. Beta1 integrin-mediated T cell adhesion and cell spreading are regulated by calpain. Exp Cell Res. 2000;261(1):260–70.

    Article  PubMed  CAS  Google Scholar 

  52. Chen J, Ganguly A, Mucsi AD, Meng J, Yan J, Detampel P, et al. Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy. J Exp Med. 2017;214(2):327–38.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Wan F, Letavernier E, Le Saux CJ, Houssaini A, Abid S, Czibik G, et al. Calpastatin overexpression impairs postinfarct scar healing in mice by compromising reparative immune cell recruitment and activation. Am J Physiol Heart Circ Physiol. 2015;309(11):H1883–93.

    Article  PubMed  CAS  Google Scholar 

  54. Witkowski JM, Bryl E. Paradoxical age-related cell cycle quickening of human CD4(+) lymphocytes: a role for cyclin D1 and calpain. Exp Gerontol. 2004;39(4):577–85.

    Article  PubMed  CAS  Google Scholar 

  55. Smith AW, Doonan BP, Tyor WR, Abou-Fayssal N, Haque A, Banik NL. Regulation of Th1/Th17 cytokines and IDO gene expression by inhibition of calpain in PBMCs from MS patients. J Neuroimmunol. 2011;232(1–2):179–85.

    Article  PubMed  CAS  Google Scholar 

  56. Selliah N, Brooks WH, Roszman TL. Proteolytic cleavage of alpha-actinin by calpain in T cells stimulated with anti-CD3 monoclonal antibody. J Immunol. 1996;156(9):3215–21.

    Article  PubMed  CAS  Google Scholar 

  57. Witkowski JM, Zmuda-Trzebiatowska E, Swiercz JM, Cichorek M, Ciepluch H, Lewandowski K, et al. Modulation of the activity of calcium-activated neutral proteases (calpains) in chronic lymphocytic leukemia (B-CLL) cells. Blood. 2002;100(5):1802–9.

    Article  PubMed  CAS  Google Scholar 

  58. Mikosik A, Henc I, Ruckemann-Dziurdzinska K, Frackowiak JE, Ploszynska A, Balcerska A, et al. Increased mu-Calpain activity in blasts of common B-precursor childhood acute lymphoblastic leukemia correlates with their lower susceptibility to apoptosis. PLoS One. 2015;10(8):e0136615.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Nassar D, Letavernier E, Baud L, Aractingi S, Khosrotehrani K. Calpain activity is essential in skin wound healing and contributes to scar formation. PLoS One. 2012;7(5):e37084.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Mikosik A, Jasiulewicz A, Daca A, Henc I, Frackowiak JE, Ruckemann-Dziurdzinska K, et al. Roles of calpain-calpastatin system (CCS) in human T cell activation. Oncotarget. 2016;7(47):76479–95.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Noma H, Kato T, Fujita H, Kitagawa M, Yamano T, Kitagawa S. Calpain inhibition induces activation of the distinct signalling pathways and cell migration in human monocytes. Immunology. 2009;128(1 Suppl):e487–96.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Ji J, Su L, Liu Z. Critical role of calpain in inflammation. Biomed Rep. 2016;5(6):647–52.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Goldmann O, Sastalla I, Wos-Oxley M, Rohde M, Medina E. Streptococcus pyogenes induces oncosis in macrophages through the activation of an inflammatory programmed cell death pathway. Cell Microbiol. 2009;11(1):138–55.

    Article  PubMed  CAS  Google Scholar 

  64. Rana T, Misra S, Mittal MK, Farrow AL, Wilson KT, Linton MF, et al. Mechanism of down-regulation of RNA polymerase III-transcribed non-coding RNA genes in macrophages by Leishmania. J Biol Chem. 2011;286(8):6614–26.

    Article  PubMed  CAS  Google Scholar 

  65. P.S. de Sousa Araújo, S.S.C. de Oliveira, C.M. d’Avila-Levy, A.L.S. dos Santos, M.H. Branquinha, Susceptibility of promastigotes and intracellular amastigotes from distinct Leishmania species to the calpain inhibitor MDL28170, Parasitol Res, 117 (7) (2018) 2085–2094.

  66. Cirone M. EBV and KSHV infection Dysregulates autophagy to optimize viral replication, prevent immune recognition and promote tumorigenesis. Viruses. 2018;10(11).

  67. Takano E, Park YH, Kitahara A, Yamagata Y, Kannagi R, Murachi T. Distribution of calpains and calpastatin in human blood cells. Biochem Int. 1988;16(3):391–5.

    PubMed  CAS  Google Scholar 

  68. Miyazaki T, Koya T, Kigawa Y, Oguchi T, Lei XF, Kim-Kaneyama JR, et al. Calpain and atherosclerosis. J Atheroscler Thromb. 2013;20(3):228–37.

    Article  PubMed  CAS  Google Scholar 

  69. T. Miyazaki, K. Tonami, S. Hata, T. Aiuchi, K. Ohnishi, X.-F. Lei, J.-r. Kim-Kaneyama, M. Takeya, H. Itabe, H. Sorimachi, H. Kurihara, A. Miyazaki, Calpain-6 confers atherogenicity to macrophages by dysregulating pre-mRNA splicing, J Clin Investig, 126 (9) (2016) 3417–3432.

  70. Wang N, Chen W, Linsel-Nitschke P, Martinez LO, Agerholm-Larsen B, Silver DL, et al. A PEST sequence in ABCA1 regulates degradation by calpain protease and stabilization of ABCA1 by apoA-I. J Clin Invest. 2003;111(1):99–107.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Hori N, Hayashi H, Sugiyama Y. Calpain-mediated cleavage negatively regulates the expression level of ABCG1. Atherosclerosis. 2011;215(2):383–91.

    Article  PubMed  CAS  Google Scholar 

  72. Yang X, Yin M, Yu L, Lu M, Wang H, Tang F, et al. Simvastatin inhibited oxLDL-induced proatherogenic effects through calpain-1-PPARgamma-CD36 pathway. Can J Physiol Pharmacol. 2016;94(12):1336–43.

    Article  PubMed  CAS  Google Scholar 

  73. Lokuta MA, Nuzzi PA, Huttenlocher A. Calpain regulates neutrophil chemotaxis. Proc Natl Acad Sci U S A. 2003;100(7):4006–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Dewitt S, Francis RJ, Hallett MB. Ca(2)(+) and calpain control membrane expansion during the rapid cell spreading of neutrophils. J Cell Sci. 2013;126(Pt 20):4627–35.

    PubMed  PubMed Central  CAS  Google Scholar 

  75. Roberts RE, Hallett MB. Neutrophil cell shape change: mechanism and Signalling during cell spreading and phagocytosis. Int J Mol Sci. 2019;20(6).

  76. Lewis KJ, Masterman B, Laffafian I, Dewitt S, Campbell JS, Hallett MB. Minimal impact electro-injection of cells undergoing dynamic shape change reveals calpain activation. Biochim Biophys Acta. 2014;1843(6):1182–7.

    Article  PubMed  CAS  Google Scholar 

  77. Ishak R, Hallett MB. Defective rapid cell shape and transendothelial migration by calpain-1 null neutrophils. Biochem Biophys Res Commun. 2018;506(4):1065–70.

    Article  PubMed  CAS  Google Scholar 

  78. Liu D, Yan Z, Minshall RD, Schwartz DE, Chen Y, Hu G. Activation of calpains mediates early lung neutrophilic inflammation in ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2012;302(4):L370–9.

    Article  PubMed  CAS  Google Scholar 

  79. Xu E, Chen J, Wang Y, Ke Z, Luo S, Zou Z. A phosphoproteomic study reveals shp-1 cleavage reprograms LPS signaling via a PI-3K/NF-kappaB and mTORC1 related mechanism. J Proteome. 2015;128:30–8.

    Article  CAS  Google Scholar 

  80. White MM, Geraghty P, Hayes E, Cox S, Leitch W, Alfawaz B, et al. Neutrophil membrane cholesterol content is a key factor in cystic fibrosis lung disease. EBioMedicine. 2017;23:173–84.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Wiemer AJ, Lokuta MA, Surfus JC, Wernimont SA, Huttenlocher A. Calpain inhibition impairs TNF-alpha-mediated neutrophil adhesion, arrest and oxidative burst. Mol Immunol. 2010;47(4):894–902.

    Article  PubMed  CAS  Google Scholar 

  82. Campbell JS, Hallett MB. Active calpain in phagocytically competent human neutrophils: electroinjection of fluorogenic calpain substrate. Biochem Biophys Res Commun. 2015;457(3):341–6.

    Article  PubMed  CAS  Google Scholar 

  83. Kumar V, Everingham S, Hall C, Greer PA, Craig AW. Calpains promote neutrophil recruitment and bacterial clearance in an acute bacterial peritonitis model. Eur J Immunol. 2014;44(3):831–41.

    Article  PubMed  CAS  Google Scholar 

  84. Tanabe F, Kasai H, He L, Kin T, Fujikado T, Kumamoto T, et al. Improvement of deficient natural killer activity and delayed bactericidal activity by a thiol proteinase inhibitor, E-64-d, in leukocytes from Chediak-Higashi syndrome patients in vitro. Int Immunopharmacol. 2009;9(3):366–70.

    Article  PubMed  CAS  Google Scholar 

  85. Gosswein S, Lindemann A, Mahajan A, Maueroder C, Martini E, Patankar J, et al. Citrullination licenses Calpain to Decondense nuclei in neutrophil extracellular trap formation. Front Immunol. 2019;10:2481.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Wang GJ, Wang Y, Teng YS, Sun FL, Xiang H, Liu JJ, et al. Protective effects of Emodin-induced neutrophil apoptosis via the Ca(2+)-Caspase 12 pathway against SIRS in rats with severe acute pancreatitis. Biomed Res Int. 2016;2016:1736024.

    Article  PubMed  PubMed Central  Google Scholar 

  87. van Raam BJ, Drewniak A, Groenewold V, van den Berg TK, Kuijpers TW. Granulocyte colony-stimulating factor delays neutrophil apoptosis by inhibition of calpains upstream of caspase-3. Blood. 2008;112(5):2046–54.

    Article  PubMed  PubMed Central  Google Scholar 

  88. McCracken J, Kinkead L, McCaffrey R, Allen L. Francisella tularensis modulates a distinct subset of regulatory factors and sustains mitochondrial integrity to impair human neutrophil apoptosis. Journal of innate immunity. 2016;8(3):299–313.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Francis RJ, Kotecha S, Hallett MB. Ca2+ activation of cytosolic calpain induces the transition from apoptosis to necrosis in neutrophils with externalized phosphatidylserine. J Leukoc Biol. 2013;93(1):95–100.

    Article  PubMed  CAS  Google Scholar 

  90. Francis RJ, Butler RE, Stewart GR. Mycobacterium tuberculosis ESAT-6 is a leukocidin causing Ca2+ influx, necrosis and neutrophil extracellular trap formation. Cell Death Dis. 2014;5:e1474.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Clement CC, Santambrogio L. The lymph self-antigen repertoire. Front Immunol. 2013;4:424.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Calle Y, Carragher NO, Thrasher AJ, Jones GE. Inhibition of calpain stabilises podosomes and impairs dendritic cell motility. J Cell Sci. 2006;119(Pt 11):2375–85.

    Article  PubMed  CAS  Google Scholar 

  93. Chou HC, Anton IM, Holt MR, Curcio C, Lanzardo S, Worth A, et al. WIP regulates the stability and localization of WASP to podosomes in migrating dendritic cells. Curr Biol. 2006;16(23):2337–44.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Sorrentino R, Terlizzi M, Di Crescenzo VG, Popolo A, Pecoraro M, Perillo G, et al. Human lung cancer-derived immunosuppressive plasmacytoid dendritic cells release IL-1alpha in an AIM2 inflammasome-dependent manner. Am J Pathol. 2015;185(11):3115–24.

    Article  PubMed  CAS  Google Scholar 

  95. Hamel-Cote G, Gendron D, Rola-Pleszczynski M, Stankova J. Regulation of platelet-activating factor-mediated protein tyrosine phosphatase 1B activation by a Janus kinase 2/calpain pathway. PLoS One. 2017;12(7):e0180336.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Meephansan J, Tsuda H, Komine M, Tominaga S, Ohtsuki M. Regulation of IL-33 expression by IFN-gamma and tumor necrosis factor-alpha in normal human epidermal keratinocytes. J Invest Dermatol. 2012;132(11):2593–600.

    Article  PubMed  CAS  Google Scholar 

  97. Wu Z, Chen X, Liu F, Chen W, Wu P, Wieschhaus AJ, et al. Calpain-1 contributes to IgE-mediated mast cell activation. J Immunol. 2014;192(11):5130–9.

    Article  PubMed  CAS  Google Scholar 

  98. Selvakumar GP, Ahmed ME, Thangavel R, Kempuraj D, Dubova I, Raikwar SP, et al. A role for glia maturation factor dependent activation of mast cells and microglia in MPTP induced dopamine loss and behavioural deficits in mice. Brain Behav Immun. 2020;87:429–43.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  99. Forsythe P, Befus AD. Inhibition of calpain is a component of nitric oxide-induced down-regulation of human mast cell adhesion. J Immunol. 2003;170(1):287–93.

    Article  PubMed  CAS  Google Scholar 

  100. Hendry L, John S. Regulation of STAT signalling by proteolytic processing. Eur J Biochem. 2004;271(23–24):4613–20.

    Article  PubMed  CAS  Google Scholar 

  101. Blom W, de Bont H, Mulder G, Nagelkerke J. The role of calpains in apoptotic changes in isolated hepatocytes after attack by natural killer cells. Environ Toxicol Pharmacol. 2002;11:159–65.

    Article  PubMed  CAS  Google Scholar 

  102. Shenoy AM, Brahmi Z. Inhibition of the calpain-mediated proteolysis of protein kinase C enhances lytic activity in human NK cells. Cell Immunol. 1991;138(1):24–34.

    Article  PubMed  CAS  Google Scholar 

  103. Tanabe F, Cui S, Ito M. Abnormal down-regulation of PKC is responsible for giant granule formation in fibroblasts from CHS (beige) mice--a thiol proteinase inhibitor, E-64-d, prevents giant granule formation in beige fibroblasts. J Leukoc Biol. 2000;67(5):749–55.

    Article  PubMed  CAS  Google Scholar 

  104. Cui S, Tanabe F, Terunuma H, Iwatani Y, Nunoi H, Agematsu K, et al. A thiol proteinase inhibitor, E-64-d, corrects the abnormalities in concanavalin a cap formation and the lysosomal enzyme activity in leucocytes from patients with Chediak-Higashi syndrome by reversing the down-regulated protein kinase C activity. Clin Exp Immunol. 2001;125(2):283–90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Mikosik A, Zaremba A, Puchalska Z, Daca A, Smolenska Z, Lopatniuk P, et al. Ex vivo measurement of calpain activation in human peripheral blood lymphocytes by detection of immunoreactive products of calpastatin degradation. Folia Histochem Cytobiol. 2007;45(4):343–7.

    PubMed  CAS  Google Scholar 

  106. Mikosik A, Foerster J, Jasiulewicz A, Frackowiak J, Colonna-Romano G, Bulati M, et al. Expression of calpain-calpastatin system (CCS) member proteins in human lymphocytes of young and elderly individuals; pilot baseline data for the CALPACENT project. Immun Ageing. 2013;10(1):27.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Salazar AM, Panico P, Burns AL, Diaz-Villasenor A, Torres-Arellano JM, Juarez-Najera A, et al. Calpain activity in leukocytes is associated with diabetes biochemical markers. Arch Med Res. 2019;50(7):451–60.

    Article  PubMed  CAS  Google Scholar 

  108. Svensson L, McDowall A, Giles KM, Stanley P, Feske S, Hogg N. Calpain 2 controls turnover of LFA-1 adhesions on migrating T lymphocytes. PLoS One. 2010;5(11):e15090.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Babich A, Burkhardt JK. Coordinate control of cytoskeletal remodeling and calcium mobilization during T-cell activation. Immunol Rev. 2013;256(1):80–94.

    Article  PubMed  CAS  Google Scholar 

  110. Lim D, Lu Y, Rudd CE. Non-cleavable Talin rescues defect in the T-cell conjugation of T-cells deficient in the immune adaptor SKAP1. Immunol Lett. 2016;172:40–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. Iguchi-Hashimoto M, Usui T, Yoshifuji H, Shimizu M, Kobayashi S, Ito Y, et al. Overexpression of a minimal domain of calpastatin suppresses IL-6 production and Th17 development via reduced NF-kappaB and increased STAT5 signals. PLoS One. 2011;6(10):e27020.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Gasperi V, Rapino C, Battista N, Bari M, Mastrangelo N, Angeletti S, et al. A functional interplay between 5-lipoxygenase and mu-calpain affects survival and cytokine profile of human Jurkat T lymphocyte exposed to simulated microgravity. Biomed Res Int. 2014;2014:782390.

    Article  PubMed  PubMed Central  Google Scholar 

  113. Paul DS, Harmon AW, Winston CP, Patel YM. Calpain facilitates GLUT4 vesicle translocation during insulin-stimulated glucose uptake in adipocytes. Biochem J. 2003;376(Pt 3):625–32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Panico P, Juarez-Najera A, Iturriaga-Goyon E, Ostrosky-Wegman P, Salazar AM. Arsenic impairs GLUT1 trafficking through the inhibition of the calpain system in lymphocytes. Toxicol Appl Pharmacol. 2019;380:114700.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by National Natural Science Foundation of China (Grant Nos.81671567, 81871244 and 81771756), Jiangsu Province “333” project (BRA2018016), Social development Foundation of Jiangsu Province (BE2019700), Chinese Postdoctoral Science Foundation (2018 M642187), Social development Foundation of Zhenjiang (SH2019076).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fang Liu.

Ethics declarations

Conflict of interest disclosure

The authors declare no commercial or financial conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, Y., Su, Z. & Liu, F. Effects of functionally diverse calpain system on immune cells. Immunol Res 69, 8–17 (2021). https://doi.org/10.1007/s12026-021-09177-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-021-09177-5

Keywords

Navigation