Skip to main content
SpringerLink
Log in

TNFα receptor genotype influences smoking-induced muscle-fibre-type shift and atrophy in mice

  • Original Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Systemic manifestations of chronic obstructive pulmonary disease (COPD) include muscle wasting, and tumour necrosis factor α (TNFα) could represent a major inducer of these processes. We studied skeletal muscle histology in a murine model of cigarette smoke (CS)-induced COPD, comparing mice with different TNFα receptor genotypes. Muscles from hind limbs of wild type (WT), TNFα receptor 1 knockout (TNFαR1KO) and TNFαR2KO mice were prepared and weighed. The lower body weight, which was observed in CS-exposed WT and TNFαR1KO mice, was paralleled by reduced weights of gastrocnemius and biceps femoris muscle. The gastrocnemius muscle was evaluated for muscle fibre apoptosis and atrophy, and fibre-type distribution. CS-induced apoptosis was observed in all genotypes, while a significant reduction of cross-sectional areas of myofibres was present only in TNFαR2KO mice. A CS-induced fibre-type shift from the IIa to the IIb phenotype was observed in WT mice, an increase of muscle-fibre-type IIx was noticed in CS-exposed TNFαR2KO mice. Our data suggest that the skeletal muscle manifestations associated with this murine COPD model are under complex regulation by both TNFα receptors, but that TNFαR2 may be the most important determinant for the outcome of CS-induced myofibre apoptosis.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Agusti AGN, Sauleda J, Miralles C, Gomez C, Togores B, Sala E, Batle S, Busquets X (2002) Skeletal muscle apoptosis and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 166:485–489

    Article  PubMed  Google Scholar 

  2. Allen DL, Linderman JK, Roy RR, Bigbee AJ, Grindeland RE, Mukku V, Edgerton VR (1997) Apoptosis: a mechanism contributing to remodeling of skeletal muscle in response to hindlimb unweighting. Cell Physiol 42:C579–C587

    Google Scholar 

  3. Andreeta F, Bernasconi P, Torchiana E, Baggi F, Cornelio F, Mantegazza R (1995) T-cell infiltration in polymyositis is characterized by coexpression of cytotoxic and T-cell-activating cytokine transcripts. Ann N Y Acad Sci 756:418–420

    Article  Google Scholar 

  4. Anthonisen NR, Connet JE, Enright PL, Manfreda J (2002) Hospitalizations and mortality in the Lung Health Study. Am J Respir Crit Care Med 166:333–339

    Article  PubMed  Google Scholar 

  5. Bernard S, LeBlanc P, Whittom F, Carrier G, Jobin J, Belleau R, Maltais F (1998) Peripheral muscle weakness in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 158:629–634

    PubMed  CAS  Google Scholar 

  6. Beutler B, Cerami A (1988) Tumor necrosis, cachexia, shock and inflammation: a common mediator. Annu Rev Biochem 57:505–518

    Article  PubMed  CAS  Google Scholar 

  7. Brusselle GG, Bracke KR, Maes T, D’Hulst AI, Moerloose KB, Joos GF, Pauwels RA (2006) Murine models of COPD. Pulm Pharmacol Ther 19:155–165

    Article  PubMed  CAS  Google Scholar 

  8. Debigare R, Cote CH, Maltais F (2001) Peripheral muscle wasting in chronic obstructive pulmonary disease: clinical relevance and mechanisms. Am J Respir Crit Care Med 164:1712–1717

    PubMed  CAS  Google Scholar 

  9. De Bleecker JL, Meire VI, Declercq W, Van Aken EH (1999) Immunolocalization of tumor necrosis factor-alpha and its receptors in inflammatory myopathies. Neuromuscul Disord 9:239–246

    Article  PubMed  Google Scholar 

  10. De Paepe B, Creus KK, D’hose S, Brusselle G, De Bleecker JL (2007) TNFα receptor signalling influences the expression of myosin heavy chain isoforms in musculus gastrocnemius of the mouse. Neuromuscul Disord 17:896

    Google Scholar 

  11. D’hulst AI, Vermaelen KY, Brusselle GG, Joos GF, Pauwels RA (2005) Time course of cigarette smoke-induced pulmonary inflammation in mice. Eur Respir J 26:204–213

    Article  PubMed  CAS  Google Scholar 

  12. D’hulst AI, Bracke KR, Maes T, De Bleecker JL, Pauwels RA, Joos GF, Brusselle GG (2006) Role of TNFα receptor 2 in cigarette smoke-induced pulmonary inflammation and emphysema. Eur Respir J 28:102–112

    Article  PubMed  CAS  Google Scholar 

  13. DiFrancia M, Barbier D, Mege JL, Orehek J (1994) Tumor necrosis factor-alpha levels and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 150:1453–1455

    CAS  Google Scholar 

  14. Gosker HR, Kubat B, Schaart G, van der Vuss GJ, Wouters EFM, Schols AMWJ (2003) Myopathological features in skeletal muscle of patients with chronic obstructive pulmonary disease. Eur Respir J 22:280–285

    Article  PubMed  CAS  Google Scholar 

  15. Gosker HR, Zeegers MP, Wouters EFM, Schols AMWJ (2007) Muscle fibre type shifting in the vastus lateralis of patients with COPD is associated with disease severity: a systematic review and meta-analysis. Thorax 62:944–949

    Article  PubMed  Google Scholar 

  16. Keatings VM, Cave SJ, Henry MJ, Morgan K, O’Connor CM, FitzGerald MX, Kalsheker N (2000) A polymorphism in the tumor necrosis factor-α gene promoter region may predispose to a poor prognosis in COPD. Chest 118:971–975

    Article  PubMed  CAS  Google Scholar 

  17. Larsson L, Orlander J, Ansveld T, Edstrom L (1988) Effects of chronic nicotine exposure on contractile enzyme-histochemical and biochemical properties of fast- and slow-twitch skeletal muscles in the rat. Acta Physiol Scand 134:519–527

    Article  PubMed  CAS  Google Scholar 

  18. Lucas CA, Kang LHD, Hoh JFY (2000) Monospecific antibodies against the three mammalian fast limb myosin heavy chains. Biochem Biophys Res Commun 272:303–308

    Article  PubMed  CAS  Google Scholar 

  19. Lundberg I, Brengman JM, Engel AG (1995) Analysis of cytokine expression in muscle in inflammatory myopathies, Duchenne dystrophy, and non-weak controls. J Neuroimmunol 63:9–16

    Article  PubMed  CAS  Google Scholar 

  20. MacEwan DJ (2002) TNF receptor subtype signalling: differences and cellular consequences. Cell Signal 14:477–492

    Article  PubMed  CAS  Google Scholar 

  21. Nakatani T, Nakashima T, Kita T, Ishihara A (2003) Effects of exposure to cigarette smoke at different dose levels on extensor digitorum longus muscle fibres in Wistar-Kyoto and spontaneously hypertensive rats. Clin Exp Pharmacol Physiol 30:671–677

    Article  PubMed  CAS  Google Scholar 

  22. Orlander J, Kiessling KH, Larsson L (1979) Skeletal muscle metabolism, morphology and function in sedentary smokers and nonsmokers. Acta Physiol Scand 107:39–46

    PubMed  CAS  Google Scholar 

  23. Pauwels R, Rabe KF (2004) Burden and clinical features of chronic obstructive pulmonary disease (COPD). The Lancet 364:613–364

    Article  Google Scholar 

  24. Peshon JJ, Torrance DS, Stocking KL, Glaccum MB, Otten C, Willis CR, Charrier K, Morrissey PJ, Ware CB, Mohler KM (1998) TNFα receptor-deficient mice reveal divergent roles for p55 and p75 in several models of inflammation. J Immunol 160:943–952

    Google Scholar 

  25. Plomgaard P, Penkowa M, Pedersen BK (2005) Fiber type specific expression of TNF-alpha, IL-6 and IL-18 in human skeletal muscles. Excer Immunol Rev 11:53–63

    Google Scholar 

  26. Saltin B, Hendriksson J, Nygaard E, Anderson P, Jansson E (1977) Fiber types and metabolic potentials of skeletal muscles in sedentary men and endurance runners. Ann N Y Acad Sci 301:3–29

    Article  PubMed  CAS  Google Scholar 

  27. Satta A, Migliori GB, Spanevello A, Neri M, Bottinelli R, Canepari M, Pelligrino MA, Reggiani C (1997) Fibre types in skeletal muscles of chronic obstructive pulmonary disease patients related to respiratory function and exercise tolerance. Eur Respir J 10:2853–2860

    Article  PubMed  CAS  Google Scholar 

  28. Schiaffino S, Gorza L, Sartore S, Saggin L, Ausoni S, Vianello M, Gundersen K, Lomo T (1989) Three myosin heavy chain isoforms in type 2 skeletal muscle fibers. J Muscle Res Cell Motil 10:197–205

    Article  PubMed  CAS  Google Scholar 

  29. Takabatake N, Nakamura H, Abe S, Inoue S, Hino T, Saito H, Yuki H, Kato S, Tomoike H (2000) The relationship between chronic hypoxemia and activation of the tumor necrosis factor-α system in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 161:1179–1184

    PubMed  CAS  Google Scholar 

  30. Tidball JG, Albrecht DE, Lokensgard BE, Spencer MJ (1995) Apoptosis precedes necrosis of dystrophin-deficient muscle. J Cell Sci 108:2197–2204

    PubMed  CAS  Google Scholar 

  31. Vescovo G, Volterrani M, Zennaro R, Sandri M, Ceconi C, Lorusso R, Ferrari R, Ambrosio GB, Dalla LL (2000) Apoptosis in the skeletal muscle of patients with heart failure: investigation of clinical and biochemical changes. Heart 84:431–437

    Article  PubMed  CAS  Google Scholar 

  32. Whittom F, Jobin J, Simard PM, Leblanc P, Simard C, Bernard S, Belleau R, Maltais F (1998) Histochemical and morphological characteristics of the vastus lateralis muscle in COPD patients. Med Sci Sports Exerc 30:1467–1474

    Article  PubMed  CAS  Google Scholar 

  33. Zador E, Mendler L, Takacs V, De Bleecker J, Wuytack F (2001) Regenerating soleus and extensor digitorum longus muscles of the rat show elevated levels of TNF-α and its receptors, TNFR-60 and TNFR-80. Muscle Nerve 24:10581067

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Christelle Snauwaert, Eliane Castrique and Evelyn Spruyt (Department of Respiratory Diseases) for skilful technical assistance, Dr. Stijn Devaere (Department of Evolutionary Morphology of Vertebrates, Ghent University) for help with the dissection of mouse skeletal muscles, and Prof. Dr. Georges Van Maele for statistical advice. The 6H1 hybridoma cell line was kindly provided by Prof. Dr. Leslie Leinwand, Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO, USA. We thank Dr. Lara Derycke (Laboratory for Experimental Oncology) for assisting with cell line cultures. This work was supported by the Fund for Scientific Research Flanders (grant G.0011.03), the concerted Research Initiative of the Ghent University (grant GOA120.50.698), the Belgian Association against Neuromuscular Disorders (ABMM), and KidAuQuai.

Author information

Authors and Affiliations

  1. Department of Neurology, Ghent University Hospital, UZ 1K12A, De Pintelaan 185, 9000 , Ghent, Belgium

    Boel De Paepe, Kim K. Creus, Sophie D’hose, Nele D’Haese & Jan L. De Bleecker

  2. Department of Respiratory Diseases, Ghent University Hospital, Ghent, Belgium

    Guy G. Brusselle, Tania Maes, Ken R. Bracke, An I. D’hulst & Guy F. Joos

Authors
  1. Boel De Paepe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guy G. Brusselle
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tania Maes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kim K. Creus
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sophie D’hose
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nele D’Haese
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ken R. Bracke
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. An I. D’hulst
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Guy F. Joos
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jan L. De Bleecker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Boel De Paepe.

Rights and permissions

Reprints and permissions

About this article

Cite this article

De Paepe, B., Brusselle, G.G., Maes, T. et al. TNFα receptor genotype influences smoking-induced muscle-fibre-type shift and atrophy in mice. Acta Neuropathol 115, 675–681 (2008). https://doi.org/10.1007/s00401-008-0348-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-008-0348-4

Keywords

Search

Navigation