Different susceptibility of elastase inhibitors to inactivation by proteinases from Staphylococcus aureus and Pseudomonas aeruginosa
Research article published in Biol Chem Hoppe Seyler (1991)
Abstract
Neutrophil elastase is thought to contribute to the lung pathology in patients with cystic fibrosis (CF). Therefore, intrapulmonary application of elastase inhibitors might be beneficial for these patients. Inactivation of such inhibitors by bacterial proteinases, however, is an important consideration in this therapy. We studied the effects of Staphylococcus aureus proteinase (STAP) and Pseudomonas aeruginosa elastase (PsE) on native (alpha 1-AT) and recombinant (rAAT) alpha 1-antitrypsin, recombinant secretory leukocyte proteinase inhibitor (rSLPI) and the leech inhibitor eglin C. All inhibitors were inactivated by these bacterial proteinases showing pronounced differences in their susceptibilities to proteolytic cleavage. Comparing the turnover rate (mol of inhibitor inactivated by one mol bacterial proteinase/min), rAAT and alpha 1-AT were approximately 20,000-fold more susceptible to STAP than rSLPI and 50,000-fold more susceptible than eglin C. Pseudomonas aeruginosa elastase inactivated all inhibitors more rapidly than STAP. rAAT and alpha 1-AT were 13-fold and 17,000-fold more susceptible than rSLPI and eglin C, respectively. Incubation of the rAAT-elastase complex with equimolar amounts of STAP did not result in release of elastase activity. Upon simultaneous addition of STAP and leukocyte elastase to rAAT, there was undisturbed elastase inhibition indicating that complex formation with elastase proceeded at a faster rate than inactivation of rAAT by the bacterial proteinase. From these results of inactivation in vitro and considering the immunogenic potential of the inhibitors studied here, we conclude that rSLPI may be the appropriate choice for anti-elastase therapy in CF.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Leech inhibitor eglin C compared to alpha-1-antitrypsin, alpha-1-antichymotrypsin, and rSLPI for susceptibility to bacterial proteinases; eglin C 50,000-fold less susceptible than alpha-1-AT.
Why This Matters for Hirudotherapy
This in-vitro study tested how readily several neutrophil-elastase inhibitors — including the leech-derived inhibitor eglin C — are inactivated by bacterial proteinases from Staphylococcus aureus and Pseudomonas aeruginosa, in the context of possible anti-elastase therapy for cystic fibrosis. Eglin C emerged as markedly more resistant to staphylococcal proteinase than alpha-1-antitrypsin (roughly 50,000-fold less susceptible), illustrating that a leech secretome protein can offer notable stability against degradative enzymes, though the authors ultimately favored rSLPI for that particular CF application. For ASH this supports the broader point that hirudo-derived inhibitors have biochemical properties (here, proteolytic robustness) worth cataloguing in the secretome drug-discovery story. Honest caveat: this is cell-free comparative biochemistry aimed at a non-leech-therapy use case (inhaled CF treatment); it draws no conclusion about leech therapy and does not demonstrate clinical efficacy.
Citation
Different susceptibility of elastase inhibitors to inactivation by proteinases from Staphylococcus aureus and Pseudomonas aeruginosa.
Sponer M et al. · Biol Chem Hoppe Seyler, 1991
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