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. Coating the matrices with HA significantly decreased elastolysis (P<0.05) induced by porcine pancreatic elastase (43%), human neutrophil elastase (53%), and human macrophage metalloelastase (80%). Concomitant in vivo studies examined the ability of an aerosol preparation of the streptococcal HA to prevent experimental emphysema induced by intratracheal administration of porcine pancreatic elastase. As seen with earlier studies involving bovine tracheal HA, a single aerosol exposure significantly decreased elastase-induced airspace enlargement, as measured by the mean linear intercept (107.5 vs 89.6 microm; P < 0. 05). Furthermore, repeated exposure to the HA aerosol for 1 month did not reveal any morphological changes in the lung. The results provide further evidence that aerosolized HA may be an effective means of preventing pulmonary emphysema and perhaps other lung diseases that involve elastic fiber injury.

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). To determine if degradation of the extracellular matrix affects lysozyme binding, hyaluronidase-treated normal lung tissues were incubated with egg white lysozyme, immunostained with the lysozyme antibody, which crossreacts with egg white lysozyme, and evaluated for degree of staining. RESULTS: Lysozyme immunostaining was significantly increased in lungs with pulmonary emphysema compared with normal or fibrotic tissues (3.4 versus 1.6 and 1.9, respectively; p < 0.05) and was preferentially associated with interstitial elastic fibres. Hyaluronidase-treated lung tissues incubated with lysozyme showed increased immunostaining for this protein compared with untreated controls (1.9 versus 1.2; p < 0.05). CONCLUSIONS: The results suggest that damage to elastic fibres and/or the surrounding extracellular matrix increases lysozyme binding. It is hypothesised that attachment of lysozyme to elastic fibres may interfere with their repair and possibly enhance the progression of pulmonary emphysema.