Lung hyaluronan levels are decreased in alpha-1 antiprotease deficiency COPD

Abstract

Introduction: Hyaluronan (HA), a long-chain polysaccharide, is currently being evaluated as a potential therapeutic agent for pulmonary emphysema, based on previous studies from this laboratory indicating its protective effect against elastic fiber breakdown. To determine whether exogenously administered HA might replace a loss of this extracellular matrix component in this disease, we measured the content of HA in lung biopsies from both healthy individuals and alpha-1 antiprotease-deficient (AAPD) COPD patients with pulmonary emphysema.

Methods: Tissue samples (9 from COPD patients, 5 from controls) were digested with papain to isolate glycosaminoglycans, and lung HA was quantified with an enzyme-linked immunoabsorbent assay.

Results: HA was significantly decreased in the AAPDCOPD population compared to normal individuals (13.5 vs 21.7 ng/mg wet lung; p < 0.01). Furthermore, there was a positive correlation between HA levels and the following parameters: 1) percent predicted FEV1 (r = 0.78; p < 0.001), 2) percent predicted DLCO (r = 0.74; p < 0.05), and 3) serum levels of AAP (r = 0.61; p < 0.05).

Conclusions: These findings support the hypothesis that depletion of lung HA plays a role in the pathogenesis of pulmonary emphysema, and that replacement of this matrix component could slow the progression of the disease.

Keywords: Alpha-1 antiprotease deficiency; COPD; Elastic fibers; Hyaluronan; Lung.