Ambivalent effects of TNF-α in myogenic cells from the quadriceps muscle of COPD patients

C. Casadevall, S. Pascual, J. M. Martínez-Llorens, P. Ausin, M. Orozco-Levi, E. Barreiro, J. Gea (Barcelona, Spain)

Source: Annual Congress 2010 - Respiratory and peripheral muscles: From basic mechanisms to altered function
Session: Respiratory and peripheral muscles: From basic mechanisms to altered function
Session type: Oral Presentation
Number: 3405
Disease area: Airway diseases

Congress or journal article abstract

Abstract

Satellite cells supply damaged or partially apoptotic fibers with new nuclei, which contribute to maintain muscle mass in their particular nuclear domain. Objective: To assess the effects of TNF-α in cultured myoblasts (the "in vitro" equivalent to satellite cells) obtained from COPD patients. Methods: Cultures of myoblasts obtained from the quadriceps muscle of severe COPD patients (FEV1, 45±6% ref.) were used. Muscle cells were separated using immunomagnetic procedures (antibodies against CD56+). This allowed a 97% myoblast content (desmin identification). Cell cultures were analyzed both under standard conditions and after blocking TNF-α receptors with neutralizing antibodies (htr9 and utr1 clones for RI and RII, respectively). Cell growth was assessed through both standard proliferation curves and BrdU incorporation assays, whereas muscle cell differentiation was evaluated using morphometric techniques. Results: Myoblasts from COPD patients showed a mean population doubling time of 3.9±0.9 days. Functional inactivation of TNF receptors resulted in a significant increase in myoblast proliferation rate conditions (RI Δ331±58%, p<0.05; RII Δ151±27%, p=0.13; and RI+RII Δ375±76%; p<0.05). By contrast, blockade of RI dramatically diminished differentiation by inhibiting myoblast fusion. Conclusion: TNF-α plays an important role in the regulation of different phases of myoblast growth and maturation



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C. Casadevall, S. Pascual, J. M. Martínez-Llorens, P. Ausin, M. Orozco-Levi, E. Barreiro, J. Gea (Barcelona, Spain). Ambivalent effects of TNF-α in myogenic cells from the quadriceps muscle of COPD patients. Eur Respir J 2010; 36: Suppl. 54, 3405

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