Involvement of LTD(4)in allergic pulmonary inflammation in mice: modulation by cysLT(1)antagonist MK-571.

Abstract

Cysteinyl leukotrienes are potent inflammatory molecules playing a major role in asthma. The involvement of these mediators in hypersensitivity in mice is not well known. This study aimed at elucidating their implication by using MK-571, a cysLT(1)receptor antagonist. Mice were sensitized with a suspension of ovalbumin (8 microg) adsorbed to alum (2 mg) and were challenged with an aerosolized ovalbumin solution (0.5%). Inflammatory cell infiltration in the bronchoalveolar lavage (mostly eosinophils) following antigen challenge was inhibited by dexamethasone (0.1, 1 and 5 mg kg(-1)s.c.) and MK-571 (1, 10, 100 mg kg(-1)i.v.) in a dose-dependent manner. Maximal inhibition was 95% with 5 mg kg(-1)dexamethasone and 90% with 100 mg kg(-1)MK-571. When injected together they showed an additive inhibitory effect on eosinophil infiltration. Bronchial hyperreactivity, measured by the increased pulmonary insufflation pressure to carbachol injections, was also inhibited dose-dependently by MK-571. The EC(50)values for carbachol were of 22.39+/-1.12 microg kg(-1)in sensitized and challenged animals that did not receive MK-571 and increased to 43.65+/-1.10, 50.12+/-1.15 and 83.18+/-1.16 microg kg(-1)in animals treated with 1, 10 and 100 mg kg(-1)MK-571 respectively. Lung microvascular leakage (as measured by Evans blue extravasation) induced by antigen bronchoprovocation was reduced by 22% after treatment with 10 mg kg(-1)MK-571. All these inhibitory effects of MK-571 suggest a role for leukotriene D(4)in this animal model of allergic asthma.

• Authors: J F Blain, P Sirois
• Journal: Prostaglandins, leukotrienes, and essential fatty acids (Prostaglandins Leukot Essent Fatty Acids) Vol. 62 Issue 6 Pg. 361-8 (Jun 2000) ISSN: 0952-3278 [Print] Scotland
• PMID: 10913229 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 Harcourt Publishers Ltd.

Chemical References

• Leukotriene Antagonists
• Membrane Proteins
• Propionates
• Quinolines
• Receptors, Leukotriene
• verlukast
• Leukotriene D4
• Dexamethasone
• Ovalbumin
• cysteinyl leukotriene receptor 2
• leukotriene D4 receptor

Topics

• Animals
• Asthma (drug therapy, immunology, physiopathology)
• Bronchial Hyperreactivity (drug therapy, physiopathology)
• Bronchial Provocation Tests
• Bronchoalveolar Lavage Fluid (chemistry)
• Capillary Permeability (drug effects)
• Dexamethasone (pharmacology)
• Disease Models, Animal
• Drug Therapy, Combination
• Leukotriene Antagonists
• Leukotriene D4 (antagonists & inhibitors, physiology)
• Male
• Membrane Proteins
• Mice
• Mice, Inbred BALB C
• Ovalbumin (immunology)
• Propionates (pharmacology, therapeutic use)
• Pulmonary Eosinophilia (drug therapy)
• Quinolines (pharmacology, therapeutic use)
• Receptors, Leukotriene