Does lysozyme play a role in the pathogenesis of COPD?

Elastic fiber injury is an important process in the pathogenesis of chronic obstructive pulmonary disease (COPD), particularly with regard to the development of pulmonary emphysema. Damage to these fibers results in uneven distribution of mechanical forces in the lung, leading to dilatation and rupture of alveolar walls. While the role of various enzymes and oxidants in this process has been well-documented, we propose that a previously unsuspected agent, lysozyme, may contribute significantly to the changes in elastic fibers observed in this disease. Studies from our laboratory have previously shown that lysozyme preferentially binds to elastic fibers in human emphysematous lungs. On the basis of this finding, it is hypothesized that the attachment of lysozyme to these fibers enhances their susceptibility to injury, and further impairs the transfer of mechanical forces in the lung, leading to increased alveolar wall damage and enhanced progression of COPD. The hypothesized effects of lysozyme are predicated on its interaction with hyaluronan (HA), a long-chain polysaccharide that is found in close proximity to elastic fibers. By preventing the binding of HA to elastic fibers in COPD, lysozyme may interfere with the protective effect of this polysaccharide against enzymes and oxidants that degrade these fibers. Furthermore, the loss of the hydrating effect of HA on these fibers may impair their elastic properties, greatly increasing the probability of their fragmentation in response to mechanical forces. The proposed hypothesis may explain why the content of HA is significantly lower in the lungs of COPD patients. It may also contribute to the design of clinical trials involving the use of exogenously administered HA as a potential treatment for COPD.