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 μg 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 μg HNE failed to enhance the severity of the SCM or emphysema induced by HNE alone. A second experiment was carried out using 50 μg 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. The failure to demonstrate enhancement of HNE-induced emphysema in the hamster by MPO system-generated oxidants instilled intratracheally does not exclude the possibility of such an enhancement in microenvironments of the lungs or under conditions in which hemorrhage is minimized.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 137-143 |
| Number of pages | 7 |
| Journal | Respiration |
| Volume | 60 |
| Issue number | 3 |
| State | Published - 1993 |
| Externally published | Yes |
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Keywords
- Hamsters
- Human neutrophil elastase
- Myeloperoxidase
- Oxidant impairment of alpha-1-protease inhibitor
- Porcine pancreatic elastase
- Pulmonary emphysema (pathophysiology)
ASJC Scopus subject areas
- Physiology
- Pulmonary and Respiratory Medicine
Cite this
Oxidants from neutrophil myeloperoxidase do not enhance elastase induced emphysema in the hamster. / Stone, P. J.; Lucey, E. C.; Breuer, R.; Christensen, T. G.; Zaslow, M. C.; Clark, Robert A; Franzblau, C.; Snider, G. L.
In: Respiration, Vol. 60, No. 3, 1993, p. 137-143.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Oxidants from neutrophil myeloperoxidase do not enhance elastase induced emphysema in the hamster
AU - Stone, P. J.
AU - Lucey, E. C.
AU - Breuer, R.
AU - Christensen, T. G.
AU - Zaslow, M. C.
AU - Clark, Robert A
AU - Franzblau, C.
AU - Snider, G. L.
PY - 1993
Y1 - 1993
N2 - 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 μg 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 μg HNE failed to enhance the severity of the SCM or emphysema induced by HNE alone. A second experiment was carried out using 50 μg 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. The failure to demonstrate enhancement of HNE-induced emphysema in the hamster by MPO system-generated oxidants instilled intratracheally does not exclude the possibility of such an enhancement in microenvironments of the lungs or under conditions in which hemorrhage is minimized.
AB - 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 μg 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 μg HNE failed to enhance the severity of the SCM or emphysema induced by HNE alone. A second experiment was carried out using 50 μg 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. The failure to demonstrate enhancement of HNE-induced emphysema in the hamster by MPO system-generated oxidants instilled intratracheally does not exclude the possibility of such an enhancement in microenvironments of the lungs or under conditions in which hemorrhage is minimized.
KW - Hamsters
KW - Human neutrophil elastase
KW - Myeloperoxidase
KW - Oxidant impairment of alpha-1-protease inhibitor
KW - Porcine pancreatic elastase
KW - Pulmonary emphysema (pathophysiology)
UR - http://www.scopus.com/inward/record.url?scp=0027183975&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027183975&partnerID=8YFLogxK
M3 - Article
C2 - 8210717
AN - SCOPUS:0027183975
VL - 60
SP - 137
EP - 143
JO - Respiration; international review of thoracic diseases
JF - Respiration; international review of thoracic diseases
SN - 0025-7931
IS - 3
ER -