Augmented muscarinic responsiveness caused by 5-lipoxygenase products secreted from alveolar macrophages in isolated-perfused rat lung

P. Padrid, R. Wolf, N. M. Munoz, S. Spaethe, Thomas Finucane, J. Solway, A. R. Leff

Research output: Contribution to journalArticle

Abstract

We examined the effect of activated alveolar macrophages (AM) on airway responsiveness to muscarinic stimulation in 33 adult Sprague-Dawley rats. An isolated-perfused lung preparation was used to ensure precise and uniform delivery of cells into peripheral airways. The bronchoconstrictor response to acetylcholine (ACh) delivered into the pulmonary arterial circulation was augmented in 8 rats after infusion of 3 x 106 AM activated with 10-6 M f- met-leu-phe and 5 μg/ml of cytochalasin B. Lung resistance (RL) caused by 10-6 mol ACh increased 2.5-fold from 0.10 ± 0.004 cm H2O/ml/s before infusion of activated AM to 0.35 ± 0.05 cm H2O/ml/s after infusion of activated AM (N = 8; p <0.05); the response to ACh was not augmented after infusion of nonactivated AM (N = 7) or vehicle control (N = 6). Baseline RL before ACh was similar in all three groups (p NS). Perfusion with activated AM also significantly increased the wet/dry (W/D) lung weight ratios (7.1 ± 0.5) compared with nonactivated AM (5.2 ± 0.1) or vehicle control (5.5 ± 0.3) (p <0.05 versus either nonactivated AM or vehicle control). A63162, a 5-lipoxygenase inhibitor, but not indomethacin, a cyclooxygenase inhibitor, completely inhibited augmentation of bronchoconstrictor responses to ACh caused by activated AM and also completely attenuated the increase in W/D lung weight ratios. A highly significant (p <0.01) correlation (R = 0.76) between W/D lung weight ratios and RL was observed after 10-6 mol ACh (the greatest dose of ACh administered). Baseline RL was equivalent for all groups before and after infusion of cells or vehicle. We demonstrate augmented muscarinic responsiveness in isolated-perfused lungs after exposure to activated AM. This augmentation occurs with the increase in the lung W/D ratio and is correlated with the magnitude of airway responsiveness. These effects of activated AM depend upon the elaboration of products of the 5- lipoxygenase pathway.

Original languageEnglish (US)
Pages (from-to)1514-1520
Number of pages7
JournalAmerican Review of Respiratory Disease
Volume147
Issue number6 I
StatePublished - 1993
Externally publishedYes

Fingerprint

Arachidonate 5-Lipoxygenase
Alveolar Macrophages
Cholinergic Agents
Lung
Acetylcholine
Pulmonary Edema
Bronchoconstrictor Agents
N-hydroxy-N-(1-(4-(phenylmethoxy)phenyl)ethyl)-acetamide
Weights and Measures
methionyl-leucyl-phenylalanine
Lipoxygenase Inhibitors
Cytochalasin B
Pulmonary Circulation
Cyclooxygenase Inhibitors
Indomethacin
Sprague Dawley Rats
Perfusion

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Augmented muscarinic responsiveness caused by 5-lipoxygenase products secreted from alveolar macrophages in isolated-perfused rat lung. / Padrid, P.; Wolf, R.; Munoz, N. M.; Spaethe, S.; Finucane, Thomas; Solway, J.; Leff, A. R.

In: American Review of Respiratory Disease, Vol. 147, No. 6 I, 1993, p. 1514-1520.

Research output: Contribution to journalArticle

Padrid, P. ; Wolf, R. ; Munoz, N. M. ; Spaethe, S. ; Finucane, Thomas ; Solway, J. ; Leff, A. R. / Augmented muscarinic responsiveness caused by 5-lipoxygenase products secreted from alveolar macrophages in isolated-perfused rat lung. In: American Review of Respiratory Disease. 1993 ; Vol. 147, No. 6 I. pp. 1514-1520.
@article{6a9e027928ac4129b5d0cde4a23b8959,
title = "Augmented muscarinic responsiveness caused by 5-lipoxygenase products secreted from alveolar macrophages in isolated-perfused rat lung",
abstract = "We examined the effect of activated alveolar macrophages (AM) on airway responsiveness to muscarinic stimulation in 33 adult Sprague-Dawley rats. An isolated-perfused lung preparation was used to ensure precise and uniform delivery of cells into peripheral airways. The bronchoconstrictor response to acetylcholine (ACh) delivered into the pulmonary arterial circulation was augmented in 8 rats after infusion of 3 x 106 AM activated with 10-6 M f- met-leu-phe and 5 μg/ml of cytochalasin B. Lung resistance (RL) caused by 10-6 mol ACh increased 2.5-fold from 0.10 ± 0.004 cm H2O/ml/s before infusion of activated AM to 0.35 ± 0.05 cm H2O/ml/s after infusion of activated AM (N = 8; p <0.05); the response to ACh was not augmented after infusion of nonactivated AM (N = 7) or vehicle control (N = 6). Baseline RL before ACh was similar in all three groups (p NS). Perfusion with activated AM also significantly increased the wet/dry (W/D) lung weight ratios (7.1 ± 0.5) compared with nonactivated AM (5.2 ± 0.1) or vehicle control (5.5 ± 0.3) (p <0.05 versus either nonactivated AM or vehicle control). A63162, a 5-lipoxygenase inhibitor, but not indomethacin, a cyclooxygenase inhibitor, completely inhibited augmentation of bronchoconstrictor responses to ACh caused by activated AM and also completely attenuated the increase in W/D lung weight ratios. A highly significant (p <0.01) correlation (R = 0.76) between W/D lung weight ratios and RL was observed after 10-6 mol ACh (the greatest dose of ACh administered). Baseline RL was equivalent for all groups before and after infusion of cells or vehicle. We demonstrate augmented muscarinic responsiveness in isolated-perfused lungs after exposure to activated AM. This augmentation occurs with the increase in the lung W/D ratio and is correlated with the magnitude of airway responsiveness. These effects of activated AM depend upon the elaboration of products of the 5- lipoxygenase pathway.",
author = "P. Padrid and R. Wolf and Munoz, {N. M.} and S. Spaethe and Thomas Finucane and J. Solway and Leff, {A. R.}",
year = "1993",
language = "English (US)",
volume = "147",
pages = "1514--1520",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "6 I",

}

TY - JOUR

T1 - Augmented muscarinic responsiveness caused by 5-lipoxygenase products secreted from alveolar macrophages in isolated-perfused rat lung

AU - Padrid, P.

AU - Wolf, R.

AU - Munoz, N. M.

AU - Spaethe, S.

AU - Finucane, Thomas

AU - Solway, J.

AU - Leff, A. R.

PY - 1993

Y1 - 1993

N2 - We examined the effect of activated alveolar macrophages (AM) on airway responsiveness to muscarinic stimulation in 33 adult Sprague-Dawley rats. An isolated-perfused lung preparation was used to ensure precise and uniform delivery of cells into peripheral airways. The bronchoconstrictor response to acetylcholine (ACh) delivered into the pulmonary arterial circulation was augmented in 8 rats after infusion of 3 x 106 AM activated with 10-6 M f- met-leu-phe and 5 μg/ml of cytochalasin B. Lung resistance (RL) caused by 10-6 mol ACh increased 2.5-fold from 0.10 ± 0.004 cm H2O/ml/s before infusion of activated AM to 0.35 ± 0.05 cm H2O/ml/s after infusion of activated AM (N = 8; p <0.05); the response to ACh was not augmented after infusion of nonactivated AM (N = 7) or vehicle control (N = 6). Baseline RL before ACh was similar in all three groups (p NS). Perfusion with activated AM also significantly increased the wet/dry (W/D) lung weight ratios (7.1 ± 0.5) compared with nonactivated AM (5.2 ± 0.1) or vehicle control (5.5 ± 0.3) (p <0.05 versus either nonactivated AM or vehicle control). A63162, a 5-lipoxygenase inhibitor, but not indomethacin, a cyclooxygenase inhibitor, completely inhibited augmentation of bronchoconstrictor responses to ACh caused by activated AM and also completely attenuated the increase in W/D lung weight ratios. A highly significant (p <0.01) correlation (R = 0.76) between W/D lung weight ratios and RL was observed after 10-6 mol ACh (the greatest dose of ACh administered). Baseline RL was equivalent for all groups before and after infusion of cells or vehicle. We demonstrate augmented muscarinic responsiveness in isolated-perfused lungs after exposure to activated AM. This augmentation occurs with the increase in the lung W/D ratio and is correlated with the magnitude of airway responsiveness. These effects of activated AM depend upon the elaboration of products of the 5- lipoxygenase pathway.

AB - We examined the effect of activated alveolar macrophages (AM) on airway responsiveness to muscarinic stimulation in 33 adult Sprague-Dawley rats. An isolated-perfused lung preparation was used to ensure precise and uniform delivery of cells into peripheral airways. The bronchoconstrictor response to acetylcholine (ACh) delivered into the pulmonary arterial circulation was augmented in 8 rats after infusion of 3 x 106 AM activated with 10-6 M f- met-leu-phe and 5 μg/ml of cytochalasin B. Lung resistance (RL) caused by 10-6 mol ACh increased 2.5-fold from 0.10 ± 0.004 cm H2O/ml/s before infusion of activated AM to 0.35 ± 0.05 cm H2O/ml/s after infusion of activated AM (N = 8; p <0.05); the response to ACh was not augmented after infusion of nonactivated AM (N = 7) or vehicle control (N = 6). Baseline RL before ACh was similar in all three groups (p NS). Perfusion with activated AM also significantly increased the wet/dry (W/D) lung weight ratios (7.1 ± 0.5) compared with nonactivated AM (5.2 ± 0.1) or vehicle control (5.5 ± 0.3) (p <0.05 versus either nonactivated AM or vehicle control). A63162, a 5-lipoxygenase inhibitor, but not indomethacin, a cyclooxygenase inhibitor, completely inhibited augmentation of bronchoconstrictor responses to ACh caused by activated AM and also completely attenuated the increase in W/D lung weight ratios. A highly significant (p <0.01) correlation (R = 0.76) between W/D lung weight ratios and RL was observed after 10-6 mol ACh (the greatest dose of ACh administered). Baseline RL was equivalent for all groups before and after infusion of cells or vehicle. We demonstrate augmented muscarinic responsiveness in isolated-perfused lungs after exposure to activated AM. This augmentation occurs with the increase in the lung W/D ratio and is correlated with the magnitude of airway responsiveness. These effects of activated AM depend upon the elaboration of products of the 5- lipoxygenase pathway.

UR - http://www.scopus.com/inward/record.url?scp=0027310923&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027310923&partnerID=8YFLogxK

M3 - Article

C2 - 8503563

AN - SCOPUS:0027310923

VL - 147

SP - 1514

EP - 1520

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 6 I

ER -