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 e nlargement 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 show n that such attachment actually prevents damage to the fibers. In the curre nt study, cell-free radiolabeled extracellular matrices, derived from rat p leural mesothelial cells, were used to test the ability of low molecular we ight (approximate to 100 kDa) streptococcal HA to prevent elastolysis, Coat ing the matrices with HA significantly decreased elastolysis (P<0.05) induc ed by porcine pancreatic elastase (43%), human neutrophil elastase (53%), a nd human macrophage metalloelastase (80%), Concomitant in vivo studies exam ined the ability of an aerosol preparation of the streptococcal HA to preve nt experimental emphysema Induced by intratracheal administration of porcin e pancreatic elastase. As seen with earlier studies involving bovine trache al HA, a single aerosol exposure significantly decreased elastase-induced a irspace enlargement, as measured by the mean linear intercept (107.5 vs 89. 6 pm; P < 0.05). Furthermore, repeated exposure to the HA aerosol for 1 mon th did not reveal any morphological changes in the lung, The results provid e further evidence that aerosolized HA may be an effective means of prevent ing pulmonary emphysema and perhaps other lung diseases that involve elasti c fiber injury.