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Oxidants from neutrophil myeloperoxidase do not enhance elastase-induced emphysema in the hamster
P J Stone1, E C Lucey, R Breuer
1Department of Biochemistry, Boston University School of Medicine, Mass 02118.
Abstract:
Alpha-1-protease inhibitor is susceptible to oxidative impairment by the neutrophil myeloperoxidase (MPO) system. The purpose of this study was to assess the effect of the MPO oxidant system on elastase-induced emphysema in the hamster. Intratracheal instillation of 200 micrograms of human neutrophil elastase (HNE) induced a significant secretory cell metaplasia (SCM) and airspace enlargement [23% increase in mean linear intercept (MLI) as compared with control values]. Instillation of MPO system components [0.6 international units (U) of MPO, 5.5 U of glucose oxidase and glucose (0.02 M)] along with 200 micrograms HNE failed to enhance the severity of the SCM or emphysema induced by HNE alone. A second experiment was carried out using 50 micrograms of porcine pancreatic elastase (PPE) to induce emphysema. PPE produced a significant 45% increase in MLI, but the MPO system combined with PPE failed to enhance the emphysema induced by PPE alone. The MPO system alone had no measurable effect on airspace size or SCM. In vitro studies showed that PPE was partially inactivated by the MPO system; a 56% loss of elastolytic activity occurred during a 6-min incubation of PPE with the MPO system. This may explain why the MPO system did not exacerbate PPE-induced injury, but it does not explain the lack of enhancement for HNE. A 6-minute incubation of HNE with the MPO system resulted in a nonsignificant 10% decrease of elastolytic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
The myeloperoxidase (MPO) system did not worsen emphysema in hamsters when combined with human neutrophil elastase (HNE) or porcine pancreatic elastase (PPE). While MPO inactivated PPE in vitro, it had minimal effect on HNE.
Area of Science:
- Pulmonary Medicine
- Biochemistry
- Cell Biology
Background:
- Alpha-1-protease inhibitor (A1PI) is crucial for lung protection.
- Neutrophil myeloperoxidase (MPO) system can oxidatively impair A1PI.
- The role of MPO in elastase-induced emphysema is not fully understood.
Purpose of the Study:
- To investigate the effect of the MPO oxidant system on elastase-induced emphysema in a hamster model.
- To determine if MPO exacerbates lung injury caused by human neutrophil elastase (HNE) or porcine pancreatic elastase (PPE).
Main Methods:
- Hamsters were instilled with HNE or PPE to induce emphysema.
- The MPO system components were co-administered with elastase.
- Secretory cell metaplasia (SCM) and mean linear intercept (MLI) were measured.
- In vitro elastolytic activity of PPE and HNE was assessed after MPO system incubation.
Main Results:
- HNE induced significant SCM and airspace enlargement (23% MLI increase).
- Co-administration of MPO system with HNE did not enhance emphysema.
- PPE induced significant airspace enlargement (45% MLI increase).
- Co-administration of MPO system with PPE did not enhance emphysema.
- In vitro, MPO system inactivated PPE (56% loss of activity) but minimally affected HNE (10% loss).
Conclusions:
- The MPO system did not exacerbate HNE- or PPE-induced emphysema in hamsters.
- In vitro inactivation of PPE by MPO may explain its lack of exacerbation, but the minimal effect on HNE suggests other mechanisms are involved.
- Further research is needed to clarify the interaction between MPO and HNE in lung injury.