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.

Synergistic effect of hydrogen peroxide and elastase on elastic fiber injury in vitro.

This laboratory has previously shown that hyperoxia enhances airspace enlargement in a hamster model of elastase-induced emphysema. To further understand the mechanism responsible for this finding, the effect of oxidants on elastase activity was studied in vitro, using a radiolabeled elastic fiber matrix derived from rat pleural mesothelial cells. Matrix samples were treated with either 0.

How a test for elastic fiber breakdown products in sputum could speed development of a treatment for pulmonary emphysema.

Pulmonary emphysema is a devastating disease for which there is no effective treatment. The development of therapeutic agents for this disorder has been hampered by the lack of clinical or biochemical tests which can rapidly evaluate drug efficacy. Since emphysema is associated with degradation of elastic fibers, the authors propose measuring the content of the elastin-specific amino acids, desmosine and isodesmosine, in sputum as a more immediate means of monitoring therapeutic interventions.

The effect of lysozyme on elastase-mediated injury.

Previous studies by this laboratory demonstrated that lysozyme is increased in human pulmonary emphysema, and that it preferentially binds to elastic fibers, which undergo degradation in this disease. In the current investigation, the relationship between lysozyme and elastic fiber injury was further examined, both in vitro and in vivo. The effect of exogenously administered egg-white lysozyme on pancreatic elastase-induced injury was determined using a biosynthetically radiolabeled extracellular matrix preparation mainly composed of elastic fibers.

The effect of hyaluronan on elastic fiber injury in vitro and elastase-induced airspace enlargement in vivo.

This laboratory has previously described a method of preventing air-space enlargement in experimental pulmonary emphysema using aerosolized hyaluronan (HA). Although it was found that HA preferentially binds to elastic fibers (which undergo breakdown by elastases in emphysema), it remains to be shown that such attachment actually prevents damage to the fibers. In the current study, cell-free radiolabeled extracellular matrices, derived from rat pleural mesothelial cells, were used to test the ability of low molecular weight ( approximately 100 kDa) streptococcal HA to prevent elastolysis.

Preferential binding of lysozyme to elastic fibres in pulmonary emphysema.

Background: Lysozyme is increased in inflammatory reactions and is a component of the extracellular matrix, but its possible role in lung diseases such as emphysema and interstitial fibrosis has not been investigated.

Methods: To characterise differences in lysozyme content among normal, emphysematous, and fibrotic human lungs, tissue sections obtained from necropsy specimens were immunostained with rabbit polyclonal anti-human lysozyme antibody using the labelled streptavidin-biotin peroxidase method. The immunostained sections were evaluated semi-quantitatively (grading the degree of immunostaining on a scale of 0-4).