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Activation of the lung S1P 1 receptor reduces allergen‐induced plasma leakage in mice
Author(s) -
Blé FX,
Cannet C,
Zurbruegg S,
Gérard C,
Frossard N,
Beckmann N,
Trifilieff A
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00391.x
Subject(s) - sphingosine 1 phosphate receptor , inflammation , lung , nasal administration , agonist , sphingosine 1 phosphate , receptor , immunology , pharmacology , sphingosine , infiltration (hvac) , medicine , chemistry , endocrinology , physics , thermodynamics
Background and purpose: It has been suggested that intratracheal administration of the immunomodulator, FTY720, could have anti‐inflammatory effects without causing a decrease in blood lymphocyte counts. However, the receptor responsible for this effect has not been defined. Experimental approach: We have described, in a mouse model of allergen‐induced inflammation, the use of proton magnetic resonance imaging to non‐invasively assess lung fluid accumulation and inflammation. Here, we used this model to investigate the sphingosine‐1‐phosphate (S1P) receptor responsible for the anti‐inflammatory effect of FTY720. Key results: When given intranasally, FTY720 (3 and 10 µg·kg −1 ) inhibited by approximately 50% the allergen‐induced accumulation of fluid in the lung detected by magnetic resonance imaging, but had no effect on the cellular inflammation in the airway space or on circulating blood lymphocytes. Inhibition of the infiltration of inflammatory cells into the airways was only observed at a dose of FTY720 that induced lymphopenia (100 µg·kg −1 ). Similar results were observed in S1P 3 ‐deficient mice. The effect of FTY720 was mimicked by intranasal treatment of wild‐type mice with a S1P 1 ‐specific agonist, AUY954. Conclusions and implications: Thus, in contrast to previously published work, our results suggest that systemic exposure of FTY720 is necessary to obtain an airway anti‐inflammatory effect. On the contrary, inhibition of the allergen‐induced accumulation of fluid in the lung, via activation of the S1P 1 receptor, is obtainable without systemic effects.