Sphingosine-1-phosphate Lyase Deficiency Produces a Pro-inflammatory Response While Impairing Neutrophil Trafficking

Sphingosine-1-phosphate (S1P) lyase catalyzes the degradation of S1P, a potent signaling lysosphingolipid. Mice with an inactive S1P lyase gene are impaired in the capacity to degrade S1P, resulting in highly elevated S1P levels. These S1P lyase-deficient mice have low numbers of lymphocytes and hig...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2011-03, Vol.286 (9), p.7348-7358
Main Authors: Allende, Maria L., Bektas, Meryem, Lee, Bridgin G., Bonifacino, Eliana, Kang, Jiman, Tuymetova, Galina, Chen, WeiPing, Saba, Julie D., Proia, Richard L.
Format: Article
Language:English
Subjects:
Acute-Phase Proteins - immunology
Aldehyde-Lyases - genetics
Aldehyde-Lyases - immunology
Aldehyde-Lyases - metabolism
Animals
Biomarkers - metabolism
Cell Adhesion Molecules - immunology
Cell Adhesion Molecules - metabolism
Cell Movement - immunology
G Protein-coupled Receptors (GPCR)
Hematopoiesis - immunology
Immunology
Inflammation
Inflammation - immunology
Inflammation - metabolism
Lysophospholipids - immunology
Lysophospholipids - metabolism
Mice
Mice, Knockout
Neutrophil
Neutrophils - cytology
Neutrophils - enzymology
Neutrophils - immunology
Signal Transduction - immunology
Sphingolipid
Sphingosine - analogs & derivatives
Sphingosine - immunology
Sphingosine - metabolism
Trafficking
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Sphingosine-1-phosphate (S1P) lyase catalyzes the degradation of S1P, a potent signaling lysosphingolipid. Mice with an inactive S1P lyase gene are impaired in the capacity to degrade S1P, resulting in highly elevated S1P levels. These S1P lyase-deficient mice have low numbers of lymphocytes and high numbers of neutrophils in their blood. We found that the S1P lyase-deficient mice exhibited features of an inflammatory response including elevated levels of pro-inflammatory cytokines and an increased expression of genes in liver associated with an acute-phase response. However, the recruitment of their neutrophils into inflamed tissues was impaired and their neutrophils were defective in migration to chemotactic stimulus. The IL-23/IL-17/granulocyte-colony stimulating factor (G-CSF) cytokine-controlled loop regulating neutrophil homeostasis, which is dependent on neutrophil trafficking to tissues, was disturbed in S1P lyase-deficient mice. Deletion of the S1P4 receptor partially decreased the neutrophilia and inflammation in S1P lyase-deficient mice, implicating S1P receptor signaling in the phenotype. Thus, a genetic block in S1P degradation elicits a pro-inflammatory response but impairs neutrophil migration from blood into tissues.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M110.171819