Effect of proteolytic enzymes on transepithelial solute transport
The effects of proteases on air-space clearance (AC) of small ((/sup 14/C)sucrose, 342 daltons) and large (/sup 125/I-neutral dextran, 70,000 daltons) solutes were studied in isolated, fluid-filled hamster lungs that were perfused in a nonrecirculating system. When instilled into the air spaces, porcine pancreatic elastase (0.1-0.4 mg/ml) and bovine pancreatic trypsin (BPT) (0.5-2.0 mg/ml), but neither Clostridium histolyticum collagenase (5.0 mg/ml) nor phenylmethylsulfonyl fluoride-inactivated BPT caused large increases in the AC of both tracer molecules. BPT-induced solute clearance was further characterized functionally and morphologically. The functional characteristics of solute AC under steady-state conditions did not indicate that transepithelial transport was diffusion-limited. Inhibition by millimolar concentrations of Zn/sup 2 +/ and by lung cooling, along with electron microscopic studies employing horseradish peroxidase as a macromolecule tracer, were consistent with epithelial solute transport by a vesicular mechanism (transcytosis). Solute transport from the interstitial compartment to the lung exterior was shown to occur via two pathways. By unknown mechanisms BPT caused small amounts of water to flow through an incompletely identified, extravascular pathway. In BPT-exposed lungs efflux of /sup 125/I-dextran 70 occurred almost exclusively through this pathway, whereas (/sup 14/C)sucrose was transported to the lung exterior partly through this same pathway and partly through the vasculature. The large differences in the diffusion coefficients of the two tracers may have accounted for these observed patterns of solute efflux from the lung. The possible significance of our findings to the pathogenesis of experimental emphysema are discussed.
- Research Organization:
- Veterans Administration Medical Center, Minneapolis, MN
- OSTI ID:
- 6842061
- Journal Information:
- J. Appl. Physiol.; (United States), Vol. 4
- Country of Publication:
- United States
- Language:
- English
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551001* - Physiological Systems- Tracer Techniques