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.
Cantor
J O
JO
St. Luke's-Roosevelt Institute for Health Sciences, New York, New York 10019, USA. JOCANTOR2pol.net
Shteyngart
B
B
Cerreta
J M
JM
Liu
M
M
Armand
G
G
Turino
G M
GM
D000336:Aerosols; D000818:Animals; D002474:Cell-Free System; D004547:Elastic Tissue / Q000293:injuries* / Q000378:metabolism*; D004646:Emphysema / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D004848:Epithelium; D005109:Extracellular Matrix; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019272:Leukocyte Elastase / Q000378:metabolism; D008168:Lung / Q000473:pathology; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000378:metabolism; D008970:Molecular Weight; D010196:Pancreatic Elastase / Q000378:metabolism*; D010994:Pleura / Q000166:cytology; D051381:Rats; D013291:Streptococcus / Q000737:chemistry; D013552:Swine
D000336:Aerosols; D006820:Hyaluronic Acid; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D008666:Metalloendopeptidases; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12