Different susceptibility of elastase inhibitors to inactivation by proteinases from Staphylococcus aureus and Pseudomonas aeruginosa
Research article published in Biological chemistry 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.
Resumen
Different susceptibility of elastase inhibitors to inactivation by proteinases from Staphylococcus aureus and Pseudomonas aeruginosa.
Por qué esto importa para la hirudoterapia
Este estudio in vitro examinó cómo las proteinasas bacterianas de Staphylococcus aureus (STAP) y de Pseudomonas aeruginosa (PsE) inactivan los inhibidores de elastasa, incluidos la alfa 1-antitripsina, la AAT recombinante, la SLPI recombinante y el inhibidor derivado de sanguijuela eglina C. La eglina C fue marcadamente más resistente a la inactivación por STAP que la alfa 1-AT (aproximadamente 50,000 veces), y también fue más resistente a PsE (aproximadamente 17,000 veces), si bien PsE inactivó todos los inhibidores más rápidamente que STAP. Los autores concluyeron que rSLPI podría ser la opción más adecuada para la terapia anti-elastasa en la fibrosis quística (FQ). La eglina C es un inhibidor de proteinasas derivado de sanguijuelas, lo que constituye una conexión directa con ASH. Este trabajo demuestra la robustez de un inhibidor derivado de sanguijuela frente a la proteólisis bacteriana en comparación con inhibidores endógenos humanos. No obstante, se trata de un trabajo puramente in vitro centrado en la evaluación de candidatos terapéuticos para la FQ, no en hirudoterapia, y los autores no seleccionaron la eglina C como el candidato preferido.
Citación
Different susceptibility of elastase inhibitors to inactivation by proteinases from Staphylococcus aureus and Pseudomonas aeruginosa
Sponer M et al. · Biological chemistry Hoppe-Seyler, 1991
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026