Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin-mediated mechanism

M. Scuri, R. Forteza, I. Lauredo, J. R. Sabater, Y. Botvinnikova, L. Allegra, W. M. Abraham

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Neutrophil elastase has been linked to inflammatory lung diseases such as chronic obstructive pulmonary disease, adult respiratory distress syndrome, emphysema, and cystic fibrosis. In guinea pigs, aerosol challenge with human neutrophil elastase causes bronchoconstriction, but the mechanism by which this occurs is not completely understood. Our laboratory previously showed that human neutrophil elastase releases tissue kallikrein (TK) from cultured tracheal gland cells. TK has been identified as the major kininogenase of the airway and cleaves both high- and low-molecular weight kininogen to yield lysyl-bradykinin. Because inhaled bradykinin causes bronchoconstriction and airway hyperresponsiveness in asthmatic patients and allergic sheep, we hypothesized that elastase-induced broncho-constriction could be mediated by bradykinin. To test this hypothesis, we measured lung resistance (RL) in sheep before and after inhalation of porcine pancreatic elastase (PPE) alone and after pretreatment with a bradykinin B2 antagonist (NPC-567), the specific human elastase inhibitor ICI 200,355, the histamine H1-antagonist diphenhydramine hydrochloride, the cysteinyl leukotriene 1 receptor antagonist montelukast, or the cyclooxygenase inhibitor indomethacin. Inhaled PPE (125-1,000 μg) caused a dose-dependent increase in RL. Aerosol challenge with a single 500 μg dose of PPE increased RL by 132 ± 8% over baseline. This response was blocked by pretreatment with NPC-567 and ICI-200,355 (n = 6; P < 0.001), whereas treatment with dyphenhydramine hydrochloride, montelukast, or indomethacin failed to block the PPE-induced bronchoconstriction. Consistent with pharmacological data, TK activity in bronchial lavage fluid increased 134 ± 57% over baseline (n = 5; P < 0.02). We conclude that, in sheep, PPE-induced bronchoconstriction is in part mediated by the generation of bradykinin. Our findings suggest that elastasekinin interactions may contribute to changes in bronchial tone during inflammatory diseases of the airways.

Original languageEnglish
Pages (from-to)1397-1402
Number of pages6
JournalJournal of Applied Physiology
Volume89
Issue number4
StatePublished - Oct 28 2000
Externally publishedYes

Fingerprint

Bronchoconstriction
Pancreatic Elastase
Bradykinin
Swine
montelukast
Tissue Kallikreins
Leukocyte Elastase
Sheep
Aerosols
Indomethacin
Low Molecular Weight Kininogens
Kallidin
Histamine H1 Antagonists
Leukotriene Antagonists
Diphenhydramine
Kallikreins
Cyclooxygenase Inhibitors
Adult Respiratory Distress Syndrome
Emphysema
Bronchoalveolar Lavage Fluid

Keywords

  • Asthma
  • Inflammation
  • Sheep
  • Tissue kallikrein

ASJC Scopus subject areas

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

Cite this

Scuri, M., Forteza, R., Lauredo, I., Sabater, J. R., Botvinnikova, Y., Allegra, L., & Abraham, W. M. (2000). Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin-mediated mechanism. Journal of Applied Physiology, 89(4), 1397-1402.

Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin-mediated mechanism. / Scuri, M.; Forteza, R.; Lauredo, I.; Sabater, J. R.; Botvinnikova, Y.; Allegra, L.; Abraham, W. M.

In: Journal of Applied Physiology, Vol. 89, No. 4, 28.10.2000, p. 1397-1402.

Research output: Contribution to journalArticle

Scuri, M, Forteza, R, Lauredo, I, Sabater, JR, Botvinnikova, Y, Allegra, L & Abraham, WM 2000, 'Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin-mediated mechanism', Journal of Applied Physiology, vol. 89, no. 4, pp. 1397-1402.
Scuri M, Forteza R, Lauredo I, Sabater JR, Botvinnikova Y, Allegra L et al. Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin-mediated mechanism. Journal of Applied Physiology. 2000 Oct 28;89(4):1397-1402.
Scuri, M. ; Forteza, R. ; Lauredo, I. ; Sabater, J. R. ; Botvinnikova, Y. ; Allegra, L. ; Abraham, W. M. / Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin-mediated mechanism. In: Journal of Applied Physiology. 2000 ; Vol. 89, No. 4. pp. 1397-1402.
@article{f3f6101459e64c6eacb0fe57b0ca3d90,
title = "Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin-mediated mechanism",
abstract = "Neutrophil elastase has been linked to inflammatory lung diseases such as chronic obstructive pulmonary disease, adult respiratory distress syndrome, emphysema, and cystic fibrosis. In guinea pigs, aerosol challenge with human neutrophil elastase causes bronchoconstriction, but the mechanism by which this occurs is not completely understood. Our laboratory previously showed that human neutrophil elastase releases tissue kallikrein (TK) from cultured tracheal gland cells. TK has been identified as the major kininogenase of the airway and cleaves both high- and low-molecular weight kininogen to yield lysyl-bradykinin. Because inhaled bradykinin causes bronchoconstriction and airway hyperresponsiveness in asthmatic patients and allergic sheep, we hypothesized that elastase-induced broncho-constriction could be mediated by bradykinin. To test this hypothesis, we measured lung resistance (RL) in sheep before and after inhalation of porcine pancreatic elastase (PPE) alone and after pretreatment with a bradykinin B2 antagonist (NPC-567), the specific human elastase inhibitor ICI 200,355, the histamine H1-antagonist diphenhydramine hydrochloride, the cysteinyl leukotriene 1 receptor antagonist montelukast, or the cyclooxygenase inhibitor indomethacin. Inhaled PPE (125-1,000 μg) caused a dose-dependent increase in RL. Aerosol challenge with a single 500 μg dose of PPE increased RL by 132 ± 8{\%} over baseline. This response was blocked by pretreatment with NPC-567 and ICI-200,355 (n = 6; P < 0.001), whereas treatment with dyphenhydramine hydrochloride, montelukast, or indomethacin failed to block the PPE-induced bronchoconstriction. Consistent with pharmacological data, TK activity in bronchial lavage fluid increased 134 ± 57{\%} over baseline (n = 5; P < 0.02). We conclude that, in sheep, PPE-induced bronchoconstriction is in part mediated by the generation of bradykinin. Our findings suggest that elastasekinin interactions may contribute to changes in bronchial tone during inflammatory diseases of the airways.",
keywords = "Asthma, Inflammation, Sheep, Tissue kallikrein",
author = "M. Scuri and R. Forteza and I. Lauredo and Sabater, {J. R.} and Y. Botvinnikova and L. Allegra and Abraham, {W. M.}",
year = "2000",
month = "10",
day = "28",
language = "English",
volume = "89",
pages = "1397--1402",
journal = "Journal of Applied Physiology",
issn = "8750-7587",
publisher = "American Physiological Society",
number = "4",

}

TY - JOUR

T1 - Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin-mediated mechanism

AU - Scuri, M.

AU - Forteza, R.

AU - Lauredo, I.

AU - Sabater, J. R.

AU - Botvinnikova, Y.

AU - Allegra, L.

AU - Abraham, W. M.

PY - 2000/10/28

Y1 - 2000/10/28

N2 - Neutrophil elastase has been linked to inflammatory lung diseases such as chronic obstructive pulmonary disease, adult respiratory distress syndrome, emphysema, and cystic fibrosis. In guinea pigs, aerosol challenge with human neutrophil elastase causes bronchoconstriction, but the mechanism by which this occurs is not completely understood. Our laboratory previously showed that human neutrophil elastase releases tissue kallikrein (TK) from cultured tracheal gland cells. TK has been identified as the major kininogenase of the airway and cleaves both high- and low-molecular weight kininogen to yield lysyl-bradykinin. Because inhaled bradykinin causes bronchoconstriction and airway hyperresponsiveness in asthmatic patients and allergic sheep, we hypothesized that elastase-induced broncho-constriction could be mediated by bradykinin. To test this hypothesis, we measured lung resistance (RL) in sheep before and after inhalation of porcine pancreatic elastase (PPE) alone and after pretreatment with a bradykinin B2 antagonist (NPC-567), the specific human elastase inhibitor ICI 200,355, the histamine H1-antagonist diphenhydramine hydrochloride, the cysteinyl leukotriene 1 receptor antagonist montelukast, or the cyclooxygenase inhibitor indomethacin. Inhaled PPE (125-1,000 μg) caused a dose-dependent increase in RL. Aerosol challenge with a single 500 μg dose of PPE increased RL by 132 ± 8% over baseline. This response was blocked by pretreatment with NPC-567 and ICI-200,355 (n = 6; P < 0.001), whereas treatment with dyphenhydramine hydrochloride, montelukast, or indomethacin failed to block the PPE-induced bronchoconstriction. Consistent with pharmacological data, TK activity in bronchial lavage fluid increased 134 ± 57% over baseline (n = 5; P < 0.02). We conclude that, in sheep, PPE-induced bronchoconstriction is in part mediated by the generation of bradykinin. Our findings suggest that elastasekinin interactions may contribute to changes in bronchial tone during inflammatory diseases of the airways.

AB - Neutrophil elastase has been linked to inflammatory lung diseases such as chronic obstructive pulmonary disease, adult respiratory distress syndrome, emphysema, and cystic fibrosis. In guinea pigs, aerosol challenge with human neutrophil elastase causes bronchoconstriction, but the mechanism by which this occurs is not completely understood. Our laboratory previously showed that human neutrophil elastase releases tissue kallikrein (TK) from cultured tracheal gland cells. TK has been identified as the major kininogenase of the airway and cleaves both high- and low-molecular weight kininogen to yield lysyl-bradykinin. Because inhaled bradykinin causes bronchoconstriction and airway hyperresponsiveness in asthmatic patients and allergic sheep, we hypothesized that elastase-induced broncho-constriction could be mediated by bradykinin. To test this hypothesis, we measured lung resistance (RL) in sheep before and after inhalation of porcine pancreatic elastase (PPE) alone and after pretreatment with a bradykinin B2 antagonist (NPC-567), the specific human elastase inhibitor ICI 200,355, the histamine H1-antagonist diphenhydramine hydrochloride, the cysteinyl leukotriene 1 receptor antagonist montelukast, or the cyclooxygenase inhibitor indomethacin. Inhaled PPE (125-1,000 μg) caused a dose-dependent increase in RL. Aerosol challenge with a single 500 μg dose of PPE increased RL by 132 ± 8% over baseline. This response was blocked by pretreatment with NPC-567 and ICI-200,355 (n = 6; P < 0.001), whereas treatment with dyphenhydramine hydrochloride, montelukast, or indomethacin failed to block the PPE-induced bronchoconstriction. Consistent with pharmacological data, TK activity in bronchial lavage fluid increased 134 ± 57% over baseline (n = 5; P < 0.02). We conclude that, in sheep, PPE-induced bronchoconstriction is in part mediated by the generation of bradykinin. Our findings suggest that elastasekinin interactions may contribute to changes in bronchial tone during inflammatory diseases of the airways.

KW - Asthma

KW - Inflammation

KW - Sheep

KW - Tissue kallikrein

UR - http://www.scopus.com/inward/record.url?scp=0033778870&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033778870&partnerID=8YFLogxK

M3 - Article

VL - 89

SP - 1397

EP - 1402

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

SN - 8750-7587

IS - 4

ER -