Administration of a synthetic antiprotease reduces smoke-induced lung injury

G. D. Niehaus, R. Kimura, L. D. Traber, David Herndon, J. T. Flynn, D. L. Traber

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Our previous studies suggest that a neutrophil-mediated inflammatory injury causes a major fraction of the pulmonary edema that occurs after smoke inhalation. Because activated neutrophils extrude cytotoxic proteases, the current study was conducted to evaluate the role of proteases in the pulmonary microvascular injury. Twelve sheep, instrumented for collection of lung lymph, were insufflated with cotton smoke. The sheep were treated 30 min after smoke inhalation with either gabexate mesilate (an inhibition of serine proteases) or vehicle. Smoke inhalation resulted in an increased protease activity in the lung interstitium, as evidenced by decreases in both antiprotease activity and immunoreactive α2-macroglobulin. Intravenous infusion of gabexate mesilate prevented the decrease in antiprotease activity. The protease inhibitor significantly attenuated the smoke-induced increase in transvascular fluid and protein flux, with untreated animals exhibiting 460% increases in flux compared with 180% in the inhibitor treated sheep. The protease inhibitor also eliminated the functional degradation in gas exchange that was observed in the untreated sheep. These studies strongly suggest that an increase in pulmonary proteolytic enzyme activity is responsible for a significant fraction of the degradation in microvascular integrity and gas exchange that is associated with smoke inhalation injury.

Original languageEnglish (US)
Pages (from-to)694-699
Number of pages6
JournalJournal of Applied Physiology
Volume69
Issue number2
StatePublished - 1990
Externally publishedYes

Fingerprint

Lung Injury
Protease Inhibitors
Smoke
Sheep
Peptide Hydrolases
Gabexate
Inhalation
Lung
Neutrophils
Smoke Inhalation Injury
Gases
Macroglobulins
Serine Proteases
Lymph
Pulmonary Edema
Intravenous Infusions
Wounds and Injuries
Proteins

Keywords

  • inhalation injury
  • microvascular
  • sheep

ASJC Scopus subject areas

  • Endocrinology
  • Physiology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Niehaus, G. D., Kimura, R., Traber, L. D., Herndon, D., Flynn, J. T., & Traber, D. L. (1990). Administration of a synthetic antiprotease reduces smoke-induced lung injury. Journal of Applied Physiology, 69(2), 694-699.

Administration of a synthetic antiprotease reduces smoke-induced lung injury. / Niehaus, G. D.; Kimura, R.; Traber, L. D.; Herndon, David; Flynn, J. T.; Traber, D. L.

In: Journal of Applied Physiology, Vol. 69, No. 2, 1990, p. 694-699.

Research output: Contribution to journalArticle

Niehaus, GD, Kimura, R, Traber, LD, Herndon, D, Flynn, JT & Traber, DL 1990, 'Administration of a synthetic antiprotease reduces smoke-induced lung injury', Journal of Applied Physiology, vol. 69, no. 2, pp. 694-699.
Niehaus GD, Kimura R, Traber LD, Herndon D, Flynn JT, Traber DL. Administration of a synthetic antiprotease reduces smoke-induced lung injury. Journal of Applied Physiology. 1990;69(2):694-699.
Niehaus, G. D. ; Kimura, R. ; Traber, L. D. ; Herndon, David ; Flynn, J. T. ; Traber, D. L. / Administration of a synthetic antiprotease reduces smoke-induced lung injury. In: Journal of Applied Physiology. 1990 ; Vol. 69, No. 2. pp. 694-699.
@article{790835c18ee8417ba4f35fadb5367f95,
title = "Administration of a synthetic antiprotease reduces smoke-induced lung injury",
abstract = "Our previous studies suggest that a neutrophil-mediated inflammatory injury causes a major fraction of the pulmonary edema that occurs after smoke inhalation. Because activated neutrophils extrude cytotoxic proteases, the current study was conducted to evaluate the role of proteases in the pulmonary microvascular injury. Twelve sheep, instrumented for collection of lung lymph, were insufflated with cotton smoke. The sheep were treated 30 min after smoke inhalation with either gabexate mesilate (an inhibition of serine proteases) or vehicle. Smoke inhalation resulted in an increased protease activity in the lung interstitium, as evidenced by decreases in both antiprotease activity and immunoreactive α2-macroglobulin. Intravenous infusion of gabexate mesilate prevented the decrease in antiprotease activity. The protease inhibitor significantly attenuated the smoke-induced increase in transvascular fluid and protein flux, with untreated animals exhibiting 460{\%} increases in flux compared with 180{\%} in the inhibitor treated sheep. The protease inhibitor also eliminated the functional degradation in gas exchange that was observed in the untreated sheep. These studies strongly suggest that an increase in pulmonary proteolytic enzyme activity is responsible for a significant fraction of the degradation in microvascular integrity and gas exchange that is associated with smoke inhalation injury.",
keywords = "inhalation injury, microvascular, sheep",
author = "Niehaus, {G. D.} and R. Kimura and Traber, {L. D.} and David Herndon and Flynn, {J. T.} and Traber, {D. L.}",
year = "1990",
language = "English (US)",
volume = "69",
pages = "694--699",
journal = "Journal of Applied Physiology",
issn = "8750-7587",
publisher = "American Physiological Society",
number = "2",

}

TY - JOUR

T1 - Administration of a synthetic antiprotease reduces smoke-induced lung injury

AU - Niehaus, G. D.

AU - Kimura, R.

AU - Traber, L. D.

AU - Herndon, David

AU - Flynn, J. T.

AU - Traber, D. L.

PY - 1990

Y1 - 1990

N2 - Our previous studies suggest that a neutrophil-mediated inflammatory injury causes a major fraction of the pulmonary edema that occurs after smoke inhalation. Because activated neutrophils extrude cytotoxic proteases, the current study was conducted to evaluate the role of proteases in the pulmonary microvascular injury. Twelve sheep, instrumented for collection of lung lymph, were insufflated with cotton smoke. The sheep were treated 30 min after smoke inhalation with either gabexate mesilate (an inhibition of serine proteases) or vehicle. Smoke inhalation resulted in an increased protease activity in the lung interstitium, as evidenced by decreases in both antiprotease activity and immunoreactive α2-macroglobulin. Intravenous infusion of gabexate mesilate prevented the decrease in antiprotease activity. The protease inhibitor significantly attenuated the smoke-induced increase in transvascular fluid and protein flux, with untreated animals exhibiting 460% increases in flux compared with 180% in the inhibitor treated sheep. The protease inhibitor also eliminated the functional degradation in gas exchange that was observed in the untreated sheep. These studies strongly suggest that an increase in pulmonary proteolytic enzyme activity is responsible for a significant fraction of the degradation in microvascular integrity and gas exchange that is associated with smoke inhalation injury.

AB - Our previous studies suggest that a neutrophil-mediated inflammatory injury causes a major fraction of the pulmonary edema that occurs after smoke inhalation. Because activated neutrophils extrude cytotoxic proteases, the current study was conducted to evaluate the role of proteases in the pulmonary microvascular injury. Twelve sheep, instrumented for collection of lung lymph, were insufflated with cotton smoke. The sheep were treated 30 min after smoke inhalation with either gabexate mesilate (an inhibition of serine proteases) or vehicle. Smoke inhalation resulted in an increased protease activity in the lung interstitium, as evidenced by decreases in both antiprotease activity and immunoreactive α2-macroglobulin. Intravenous infusion of gabexate mesilate prevented the decrease in antiprotease activity. The protease inhibitor significantly attenuated the smoke-induced increase in transvascular fluid and protein flux, with untreated animals exhibiting 460% increases in flux compared with 180% in the inhibitor treated sheep. The protease inhibitor also eliminated the functional degradation in gas exchange that was observed in the untreated sheep. These studies strongly suggest that an increase in pulmonary proteolytic enzyme activity is responsible for a significant fraction of the degradation in microvascular integrity and gas exchange that is associated with smoke inhalation injury.

KW - inhalation injury

KW - microvascular

KW - sheep

UR - http://www.scopus.com/inward/record.url?scp=0025148869&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025148869&partnerID=8YFLogxK

M3 - Article

C2 - 1699920

AN - SCOPUS:0025148869

VL - 69

SP - 694

EP - 699

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

SN - 8750-7587

IS - 2

ER -