The pulmonary matrix, glycosaminoglycans and pulmonary emphysema

This paper reviews recent evidence of the effect of intratracheal hyalurona n (HA) to limit the induction of experimental emphysema in hamsters. Experi mental emphysema was induced by both neutrophil and pancreatic elastase ins tilled intratracheally. Emphysema was quantified anatomically by measuremen t of alveolar mean linear intercept. Hyaluronidase, instilled intratracheal ly, enhanced the induction of experimental emphysema. Air-space size measur ed one week after intratracheal instillation of elastase showed that admini stration of 1 mg HA immediately following elastase administration resulted in a marked reduction in air-space enlargement (82 mu M vs 122 mu M, p < 0. 01). Similarly, animals given either 1 or 2 mg HA 2h before elastase or 2 m g HA Ih after elastase showed a significant decrease in air-space enlargeme nt compared to controls (96 mu M, 88 mu M vs 120 mu M and 66 mu M vs 104 mu M, respectively; p < 0.05. Experimental emphysema induced by neutrophil el astase was also limited by the administration of 1 or 4 mg of HA, administe red 2 h prior to elastase (57 and 59 mu M, respectively vs 64 for controls, p < 0.05). Characterization of administered HA showed a mean molecular wei ght of 104,800 Da, less than 5% protein and a uronic acid/ hexosamine ratio of 1, which is characteristic of HA. Studies using fluorescein-labeled hyaluronan (HA) showed fluorescence assoc iated with interstitial, pleural and vascular elastic fibers. The mechanism of attachment of the administered HA to elastin remains unknown. Fluoresce in labeling of elastin was visible for at least 4 h post-instillation These studies indicate a protective effect of hyaluronan against elastase degrad ation of pulmonary elastin h vivo by both pancreatic and neutrophil elastas es. The anatomical studies further suggest a mechanism of protective coatin g of hyaluronan which may limit access to pulmonary elastin from neutrophil s and alveolar macrophages. Results also suggest that a reduction in pulmon ary hyaluronan content increases the susceptibility of elastin to degradati on by elastases. These studies provide evidence for an antielastase effect of hyaluronan which is not dependent upon enzyme inhibition but on anatomic al protection of pulmonary elastin by other mechanisms.