TNF[alpha] receptor genotype influences smoking-induced muscle-fibre-type shift and atrophy in mice

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. [PUBLICATION ABSTRACT]