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S1P ‐induced airway smooth muscle hyperresponsiveness and lung inflammation in vivo : molecular and cellular mechanisms
Author(s) -
Roviezzo F,
Sorrentino R,
Bertolino A,
De Gruttola L,
Terlizzi M,
Pinto A,
Napolitano M,
Castello G,
D'Agostino B,
Ianaro A,
Sorrentino R,
Cirino G
Publication year - 2015
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/bph.13033
Subject(s) - immunoglobulin e , immunology , lung , mast cell , inflammation , in vivo , sphingosine 1 phosphate , sphingosine , medicine , adoptive cell transfer , chemistry , pathology , biology , immune system , antibody , t cell , receptor , microbiology and biotechnology
Background and Purpose Sphingosine‐1‐phosphate ( S1P ) has been shown to be involved in the asthmatic disease as well in preclinical mouse experimental models of this disease. The aim of this study was to understand the mechanism(s) underlying S1P effects on the lung. Experimental Approach BALB /c, mast cell‐deficient and N ude mice were injected with S1P (s.c.) on days 0 and 7. Functional, molecular and cellular studies were performed. Key Results S1P administration to BALB /c mice increased airway smooth muscle reactivity, mucus production, PGD 2 , IgE , IL ‐4 and IL ‐13 release. These features were associated to a higher recruitment of mast cells to the lung. Mast cell‐deficient K it W ‐sh/ W ‐sh mice injected with S1P did not display airway smooth muscle hyper‐reactivity. However, lung inflammation and IgE production were still present. Treatment in vivo with the anti‐ CD 23 antibody B3B4 , which blocks IgE production, inhibited both S1P ‐induced airway smooth muscle reactivity in vitro and lung inflammation. S1P administration to N ude mice did not elicit airway smooth muscle hyper‐reactivity and lung inflammation. Naïve (untreated) mice subjected to the adoptive transfer of CD 4+ T‐cells harvested from S1P ‐treated mice presented all the features elicited by S1P in the lung. Conclusions and Implications S1P triggers a cascade of events that sequentially involves T ‐cells, IgE and mast cells reproducing several asthma‐like features. This model may represent a useful tool for defining the role of S1P in the mechanism of action of currently‐used drugs as well as in the development of new therapeutic approaches for asthma‐like diseases.