Effect of azelastine on platelet-activating factor-induced microvascular leakage in rat airways

1999 ◽  
Vol 276 (2) ◽  
pp. L351-L357 ◽  
Author(s):  
Jun Tamaoki ◽  
Isao Yamawaki ◽  
Etsuko Tagaya ◽  
Mitsuko Kondo ◽  
Kazutetsu Aoshiba ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Main Bronchus ◽  
Platelet Activating Factor ◽  
Lavage Fluid ◽  
Inhibitory Effect ◽  
Mucosal Inflammation ◽  
Neutrophil Accumulation ◽  
Neutrophil Elastase Inhibitor ◽  
Elastase Inhibitor ◽  
Microvascular Leakage

To determine the effect of the antiallergic drug azelastine on airway mucosal inflammation, we studied airway microvascular permeability in response to platelet-activating factor (PAF) in pathogen-free rats. Vascular permeability and neutrophil accumulation were assessed by the percent area occupied by Monastral blue-labeled blood vessels and by myeloperoxidase-containing granulocytes, respectively, in whole mounts of the trachea and main bronchus. Intravenous PAF caused dose-dependent increases in the area density of Monastral blue-labeled vessels and neutrophil influx, and the former effect was inhibited by depletion of circulating neutrophils by cyclophosphamide or treatment with the neutrophil elastase inhibitor ONO-5046. Pretreatment with azelastine inhibited PAF-induced vascular leakage without affecting neutrophil accumulation. This inhibitory effect of azelastine was not seen in neutropenic rats and ONO-5046-treated rats. PAF increased neutrophil elastase contents in bronchoalveolar lavage fluid, an effect that was inhibited by azelastine. Therefore, azelastine attenuates PAF-induced airway mucosal microvascular leakage, probably involving inhibition of the release of neutrophil elastase from activated neutrophils.

scholarly journals Neutrophil elastase inhibitor sivelestat ameliorates gefitinib-naphthalene-induced acute pneumonitis in mice

2017 ◽  
Author(s):  
Hironori Mikumo ◽  
Toyoshi Yanagihara ◽  
Naoki Hamada ◽  
Eiji Harada ◽  
Saiko Ogata-Suetsugu ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Therapeutic Agent ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Lavage Fluid ◽  
Egfr Mutations ◽  
Airway Epithelial ◽  
Neutrophil Elastase Inhibitor ◽  
Elastase Inhibitor ◽  
Promising Therapeutic Agent

ABSTRACTBackground and objectiveGefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is an effective therapeutic agent for non-small cell lung cancer with EGFR mutations. It can cause severe acute pneumonitis in some patients. We previously demonstrated that mice with naphthalene-induced airway epithelial injury developed severe gefitinib-induced pneumonitis and that neutrophils played important roles in the development of the disease. This study aimed to investigate the effects of the neutrophil elastase inhibitor sivelestat on gefitinib-induced pneumonitis in mice.MethodsC57BL/6J mice received naphthalene (200 mg/kg) intraperitoneally on day 0. Gefitinib (250 or 300 mg/kg) was orally administered to mice from day −1 until day 13. Sivelestat (150 mg/kg) was administered intraperitoneally from day 1 until day 13. Bronchoalveolar lavage fluid (BALF) and lung tissues were sampled on day 14.ResultsSivelestat treatment significantly reduced the protein level, neutrophil count, neutrophil elastase activity in BALF, and severity of histopathologic findings on day 14 for mice administered with 250 mg/kg of gefitinib. Moreover, sivelestat treatment significantly improved the survival of mice administered with 300 mg/kg of gefitinib. Conclusions: These results indicate that sivelestat is a promising therapeutic agent for severe acute pneumonitis caused by gefitinib.Summary statementNeutrophil elastase inhibitor sivelestat is a promising therapeutic agent for severe acute pneumonitis caused by gefitinib.

Smoking accelerates absorption of inhaled neutrophil elastase inhibitor FK706

1999 ◽  
Vol 66 (5) ◽  
pp. 501-508 ◽  
Author(s):  
F KOIZUMI ◽  
M MURAKAMI ◽  
H KAGEYAMA ◽  
M KATASHIMA ◽  
M TERAKAWA ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Neutrophil Elastase Inhibitor ◽  
Elastase Inhibitor

Study on Perioperative Administration of a Neutrophil Elastase Inhibitor for Interstitial Pneumonias

2017 ◽  
Vol 103 (6) ◽  
pp. 1781-1787 ◽  
Author(s):  
Mariko Fukui ◽  
Kazuya Takamochi ◽  
Shiaki Oh ◽  
Takeshi Matsunaga ◽  
Kazuhiro Suzuki ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Neutrophil Elastase Inhibitor ◽  
Elastase Inhibitor

Platelet-activating factor contributes to acute lung leak in rats given interleukin-1 intratracheally

2000 ◽  
Vol 279 (1) ◽  
pp. L75-L80 ◽  
Author(s):  
Young M. Lee ◽  
Brooks M. Hybertson ◽  
Hyun G. Cho ◽  
Lance S. Terada ◽  
Okyong Cho ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Platelet Activating Factor ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Myeloperoxidase Activity ◽  
Cerium Chloride ◽  
Neutrophil Accumulation ◽  
Web 2086

Lung lavage fluid of patients with acute lung injury (ALI) has increased levels of interleukin-1 (IL-1) and neutrophils, but their relationship to the lung leak that characterizes these patients is unclear. To address this concern, we investigated the role of the neutrophil agonist platelet-activating factor [1- O-alkyl-2-acetyl- sn-glycero-3-phosphocholine (PAF)] in the development of the acute neutrophil-dependent lung leak that is induced by giving IL-1 intratracheally to rats. We found that PAF acetyltransferase and PAF activities increased in lungs of rats given IL-1 intratracheally compared with lungs of sham-treated rats given saline intratracheally. The participation of PAF in the development of lung leak and lung neutrophil accumulation after IL-1 administration was suggested when treatment with WEB-2086, a commonly used PAF-receptor antagonist, decreased lung leak, lung myeloperoxidase activity, and lung lavage fluid neutrophil increases in rats given IL-1 intratracheally. Additionally, neutrophils recovered from the lung lavage fluid of rats given IL-1 intratracheally reduced more nitro blue tetrazolium (NBT) in vitro than neutrophils recovered from control rats or rats that had been given WEB-2086 and then IL-1. Histological examination indicated that the endothelial cell-neutrophil interfaces of cerium chloride-stained lung sections of rats given IL-1 contained increased cerium perhydroxide (the reaction product of cerium chloride with hydrogen peroxide) compared with lungs of control rats or rats treated with WEB-2086 and then given IL-1 intratracheally. These in vivo findings were supported by parallel findings showing that WEB-2086 treatment decreased neutrophil adhesion to IL-1-treated cultured endothelial cells in vitro. We concluded that PAF contributes to neutrophil recruitment and neutrophil activation in lungs of rats given IL-1 intratracheally.

Protection Against Acute Lung Injury by Intravenous or Intratracheal Pretreatment with EPI-HNE-4, a New Potent Neutrophil Elastase Inhibitor

2002 ◽  
Vol 26 (3) ◽  
pp. 290-297 ◽  
Author(s):  
Christophe Delacourt ◽  
Sabine Hérigault ◽  
Christophe Delclaux ◽  
Alain Poncin ◽  
Micheline Levame ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Neutrophil Elastase ◽  
Neutrophil Elastase Inhibitor ◽  
Elastase Inhibitor

scholarly journals ONO-6818, a novel, potent neutrophil elastase inhibitor, reduces inflammatory mediators during simulated extracorporeal circulation

2003 ◽  
Vol 76 (4) ◽  
pp. 1234-1239 ◽  
Author(s):  
Yukihiro Yoshimura ◽  
Yuji Hiramatsu ◽  
Yukio Sato ◽  
Satoshi Homma ◽  
Yoshiharu Enomoto ◽  
...  
Keyword(s):  
Extracorporeal Circulation ◽  
Inflammatory Mediators ◽  
Neutrophil Elastase ◽  
Neutrophil Elastase Inhibitor ◽  
Elastase Inhibitor
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