Distribution of costameric proteins in the diaphragm of patients with chronic obstructive pulmonary disease.

Abstract

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with an increased load on the diaphragm. Increased (eccentric) loading has been shown to result in disturbances in the cytoskeleton. OBJECTIVES: We hypothesized that due to a continuous overload of the diaphragm in COPD patients, distinct alterations in the membrane-associated cytoskeleton occur, especially in the costameres. METHODS: Diaphragm biopsies from 7 COPD patients (forced expiratory volume in 1 s 62 +/- 3% predicted) and 5 non-COPD patients (forced expiratory volume in 1 s 105 +/- 6% predicted) were obtained. Cryosections of these biopsies were stained with antibodies against the costameric proteins of the focal adhesion complex (vinculin, talin and integrin-beta(1)), the dystroglycan complex (dystrophin and beta-dystroglycan) and the spectrin-based membrane cytoskeleton (beta-spectrin). Furthermore, in these cryosections, the basal membrane protein laminin was stained. RESULTS: We found no differences in the distribution and staining intensity of the costameric proteins of the focal adhesion complex, the dystroglycan complex and the spectrin-based membrane cytoskeleton in the diaphragm between the COPD and the non-COPD patients. Furthermore, no differences were observed in the expression of laminin in the diaphragm between COPD and non-COPD patients. CONCLUSIONS: These results indicate that the increased loading to which the diaphragm is exposed in COPD does not result in disturbances in expression of the costameric system and histological damage of the sarcolemma.