Degradation of Human α1-Antitrypsin by Hepatocyte Acid Cathepsins

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Abstract
The present study was undertaken to examine the capacity of α1-antitrypsin to act as an inhibitor or conversely as a substrate of hepatocyte lysosomal acid cathepsins, enzymes that normally break down intracellular accumulations of protein. Hepatocyte-enriched preparations from the livers of fetal, neonatal, and adult rabbits were obtained and their granule hydrolases were interacted at pH 3.0 with a fraction of human serum containing a molar excess of α1-antitrypsin. In addition, a human liver was examined in a similar way. All granule extracts tested produced degradation of human serum proteins, including α1-antitrypsin, within 1 hour as monitored by immunoelectrophoretic analysis. It was concluded that α1-antitrypsin does not inhibit hepatocyte acid cathepsins at any of the stages of liver development tested, but rather that this serum glycoprotein is degraded by these acid proteases. These results are discussed in terms of the pathogenesis of α1-antitrypsin deposits in the livers of persons with serum deficiency of this antiprotease, a condition that has been correlated with increased incidence of pulmonary emphysema.

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