Structure of the chondroitin 4-sulfate-protein linkage region. Isolation and characterization of the disaccharide 3-O-beta-D-glucuronosyl-D-galactose.
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Chemical Phenomena↗
Biomedical subjects
G Armand
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Separation of the soluble proteins of bovine lenses on polacrylamide gels.
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Animals↗
Pulmonary air-space enlargement induced by intratracheal instillment of hyaluronidase and concomitant exposure to 60% oxygen.
Although emphysema is generally characterized by damage to pulmonary elastic fibers, the causes of such injury appear to be complex and are not entirely explained by a singular imbalance between elastases and their inhibitors. Other factors could compromise elastic fiber integrity. To test the validity of this argument, hamsters were instilled intratracheally with a nonelastolytic enzyme, hyaluronidase (which reduces lung hexuronic acid content by 21% after 24 h), then exposed to an otherwise nontoxic concentration of oxygen (60%) for 4 days. Additional groups were given (1) hyaluronidase and room air, (2) saline and 60% oxygen, and (3) saline and room air. Treatment with both hyaluronidase and 60% oxygen resulted in a significant increase in air-space enlargement at 4 days (67.1 vs. 57.9 microns for saline/room air controls; p < .05), which was accompanied by only minimal inflammatory changes, as determined by both light microscopy and lavage cytology. Animals receiving either hyaluronidase or 60% oxygen alone showed no significant increases in air-space size compared to those given saline and exposed to room air. While the mechanisms responsible for these results are unclear, the marked increase in radiolabeling of lung elastin cross-links (desmosine and isodesmosine) in animals receiving both hyaluronidase and 60% oxygen (429 vs. 168 cpm/g dry lung for saline/room air controls; p < .05), as well as a significant decrease in total lung desmosine and isodesmosine (32.5 vs. 37.7 micrograms/lung for saline/room air controls; p < .05), suggests that elastic fiber damage is a potential factor. Moreover, only those animals receiving both hyaluronidase and 60% oxygen showed a significant rise in cell-free elastase activity in lavage fluids compared to saline/room air controls (83.3 vs. 48.3 ng; p < .05). On the basis of these findings, it is concluded that while elastic fiber damage may be a common pathway in emphysema, the factors that initiate the disease may be more varied than previously suspected and not always related to the balance between elastases and their inhibitors.
Animals↗
Further investigation of the use of intratracheally administered hyaluronic acid to ameliorate elastase-induced emphysema.
Previously, this laboratory has shown that intratracheally administered hyaluronic acid (HA) significantly reduces air-space enlargement in a hamster model of emphysema induced with pancreatic elastase. Whereas HA was given immediately following elastase in those initial studies, the current investigation determined the effect of instilling HA up to 2 h before or after intratracheal administration of elastase to hamsters. Both 1 and 2 mg HA, given 2 h before pancreatic elastase, significantly decreased (p < .05) air-space enlargement compared to controls (as measured by the mean linear intercept). Instillment of 2 mg HA, 1 h after pancreatic elastase, had a similar effect (p < .05). In contrast, 1 mg HA, given 1 or 2 h after pancreatic elastase, did not significantly affect the mean linear intercept. Against human neutrophil elastase, HA exhibited the same protective effect. While neutrophil elastase induced less air-space enlargement than pancreatic elastase, both 1 and 4 mg of HA, given 2 h prior to the enzyme, still produced a significant reduction (p < .05) in the mean linear intercept. HA exerted this effect despite the fact that it initiates a transient influx of neutrophils into the lung. Since HA does not slow the clearance of intratracheally instilled [14C] albumin from the lung, its mechanism of action may not involve physical interference with the movement of elastase through the lung, but may instead depend on interaction with elastic fibers. Evidence for an association between these two matrix constituents was provided by studies using fluorescein-labeled HA. Overall, these results further suggest that HA may be useful in preventing lung injury by elastases.
Air↗