Document Detail

Sphingosine-kinase 1 and 2 contribute to oral sensitization and effector phase in a mouse model of food allergy.
MedLine Citation:
PMID:  22020265     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Sphingosine-1-phosphate (S1P) influences activation, migration and death of immune cells. Further, S1P was proposed to play a major role in the induction and promotion of allergic diseases. However, to date only limited information is available on the role of S1P in food allergy.
OBJECTIVE: We aimed to investigate the role of sphingosine-kinase (SphK) 1 and 2, the enzymes responsible for endogenous S1P production, on the induction of food allergy.
METHODS AND RESULTS: Human epithelial colorectal CaCo2 cells stimulated in vitro with S1P revealed a decrease of transepithelial resistance and enhanced transport of FITC labeled OVA. We studied the effect of genetic deletion of the enzymes involved in S1P production on food allergy induction using a mouse model of food allergy based on intragastrically (i.g.) administered ovalbumin (OVA) with concomitant acid-suppression. Wild-type (WT), SphK1(-/-) and SphK2(-/-) mice immunized with OVA alone i.g. or intraperitoneally (i.p.) were used as negative or positive controls, respectively. SphK1- and SphK2-deficient mice fed with OVA under acid-suppression showed reduced induction of OVA specific IgE and IgG compared to WT mice, but had normal responses when immunized by the intraperitoneal route. Flow cytometric analysis of spleen cells revealed a significantly reduced proportion of CD4(+) effector T-cells in both SphK deficient animals after oral sensitization. This was accompanied by a reduced accumulation of mast cells in the gastric mucosa in SphK-deficient animals compared to WT mice. Furthermore, mouse mast cell protease-1 (mMCP-1) levels, an IgE-mediated anaphylaxis marker, were reliably elevated in allergic WT animals.
CONCLUSION: Modulation of the S1P homeostasis by deletion of either SphK1 or SphK2 alters the sensitization and effector phase of food allergy.
Susanne C Diesner; Ana Olivera; Sandra Dillahunt; Cornelia Schultz; Thomas Watzlawek; Elisabeth Förster-Waldl; Arnold Pollak; Erika Jensen-Jarolim; Eva Untersmayr; Juan Rivera
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2011-10-14
Journal Detail:
Title:  Immunology letters     Volume:  141     ISSN:  1879-0542     ISO Abbreviation:  Immunol. Lett.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-20     Completed Date:  2012-04-23     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  7910006     Medline TA:  Immunol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  210-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
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MeSH Terms
Administration, Oral
CD4-Positive T-Lymphocytes / immunology,  metabolism*,  pathology
Caco-2 Cells
Cell Movement / genetics
Chemokine CCL2 / genetics,  immunology,  metabolism
Disease Models, Animal
Food Hypersensitivity / diagnosis,  genetics,  immunology*
Gastric Mucosa / pathology
Immunoglobulin E / biosynthesis,  blood,  genetics
Mast Cells / immunology,  metabolism*,  pathology
Mice, Inbred Strains
Mice, Knockout
Ovalbumin / administration & dosage
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics,  immunology,  metabolism*
Protein Tyrosine Phosphatase, Non-Receptor Type 6 / genetics,  immunology,  metabolism*
Grant Support
P 21577-B11//Austrian Science Fund FWF; P 21884-B11//Austrian Science Fund FWF; ZIA AR041155-05/AR/NIAMS NIH HHS
Reg. No./Substance:
0/Ccl2 protein, mouse; 0/Chemokine CCL2; 37341-29-0/Immunoglobulin E; 9006-59-1/Ovalbumin; EC Tyrosine Phosphatase, Non-Receptor Type 11; EC Tyrosine Phosphatase, Non-Receptor Type 6
Erratum In:
Immunol Lett. 2012 Aug 30;146(1-2):79

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