Recombinant α1-proteinase inhibitor blocks antigen- and mediator-induced airway responses in sheep

Mario Scuri, Yelena Botvinnikova, Isabel T. Lauredo, William M. Abraham

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

α1-Proteinase inhibitor (α1-PI) is a natural serine protease inhibitor. Although mainly thought to protect the airways from neutrophil elastase, α1-PI may also regulate the development of airway hyperresponsiveness (AHR), as indicated by our previous findings of an inverse relationship between lung α1-PI activity and the severity of antigen-induced AHR. Because allergic stimulation of the airways causes release of elastase, tissue kallikrein, and reactive oxygen species (ROS), all of which can reduce α1-PI activity and contribute to AHR, we hypothesized that administration of exogenous α1-PI should protect against pathophysiological airway responses caused by these agents. In untreated allergic sheep, airway challenge with elastase, xanthine/xanthine oxidase (which generates ROS), high-molecular-weight kininogen, the substrate for tissue kallikrein, and antigen resulted in bronchoconstriction. ROS and antigen also induced AHR to inhaled carbachol. Treatment with 10 mg of recombinant α1-PI (rα1-PI) blocked the bronchoconstriction caused by elastase, high-molecular-weight kininogen, and ROS, and the AHR induced by ROS and antigen. One milligram of rα1-PI was ineffective. These are the first in vivo data demonstrating the effects of rα1-PI. Our results are consistent with and extend findings obtained with human plasma-derived α1-PI and suggest that α1-PI may be important in the regulation of airway responsiveness.

Original languageEnglish
Pages (from-to)1900-1906
Number of pages7
JournalJournal of Applied Physiology
Volume93
Issue number6
StatePublished - Dec 1 2002
Externally publishedYes

Fingerprint

Sheep
Peptide Hydrolases
Antigens
Reactive Oxygen Species
Pancreatic Elastase
High Molecular Weight Kininogens
Tissue Kallikreins
Bronchoconstriction
Leukocyte Elastase
Serine Proteinase Inhibitors
Xanthine
Xanthine Oxidase
Carbachol
Lung

Keywords

  • Oxygen radicals
  • Proteases

ASJC Scopus subject areas

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

Cite this

Scuri, M., Botvinnikova, Y., Lauredo, I. T., & Abraham, W. M. (2002). Recombinant α1-proteinase inhibitor blocks antigen- and mediator-induced airway responses in sheep. Journal of Applied Physiology, 93(6), 1900-1906.

Recombinant α1-proteinase inhibitor blocks antigen- and mediator-induced airway responses in sheep. / Scuri, Mario; Botvinnikova, Yelena; Lauredo, Isabel T.; Abraham, William M.

In: Journal of Applied Physiology, Vol. 93, No. 6, 01.12.2002, p. 1900-1906.

Research output: Contribution to journalArticle

Scuri, M, Botvinnikova, Y, Lauredo, IT & Abraham, WM 2002, 'Recombinant α1-proteinase inhibitor blocks antigen- and mediator-induced airway responses in sheep', Journal of Applied Physiology, vol. 93, no. 6, pp. 1900-1906.
Scuri, Mario ; Botvinnikova, Yelena ; Lauredo, Isabel T. ; Abraham, William M. / Recombinant α1-proteinase inhibitor blocks antigen- and mediator-induced airway responses in sheep. In: Journal of Applied Physiology. 2002 ; Vol. 93, No. 6. pp. 1900-1906.
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