Abstract
Despite the importance of signaling lipids, many questions remain about their function because few tools are available for charting lipid gradients in vivo. Here we generated a sphingosine 1-phosphate (S1P) reporter mouse and used this mouse to define the distribution of S1P in the spleen. Unexpectedly, the presence of blood did not serve as a predictor of the concentration of signaling-available S1P. Large areas of the red pulp had low concentrations of S1P, while S1P was sensed by cells inside the white pulp near the marginal sinus. The lipid phosphate phosphatase LPP3 maintained low S1P concentrations in the spleen and enabled efficient shuttling of marginal zone B cells. The exquisitely tight regulation of S1P availability might explain how a single lipid can simultaneously orchestrate the movements of many cells of the immune system.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Differentiation / metabolism
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B-Lymphocytes / metabolism
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Cell Line
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Lysophospholipids / metabolism*
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Macrophages / metabolism
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Mice, Knockout
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Mice, Transgenic
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Microscopy, Confocal
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Mutant Proteins / genetics
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Mutant Proteins / metabolism
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Phosphatidate Phosphatase / genetics
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Phosphatidate Phosphatase / metabolism
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Receptors, Lysosphingolipid / genetics
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Receptors, Lysosphingolipid / metabolism
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Red Fluorescent Protein
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Sialic Acid Binding Ig-like Lectin 1 / metabolism
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Sphingosine / analogs & derivatives*
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Sphingosine / metabolism
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Sphingosine-1-Phosphate Receptors
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Spleen / cytology
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Spleen / metabolism*
Substances
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Antigens, Differentiation
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Luminescent Proteins
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Lysophospholipids
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Mutant Proteins
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Receptors, Lysosphingolipid
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S1pr1 protein, mouse
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Sialic Acid Binding Ig-like Lectin 1
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Sphingosine-1-Phosphate Receptors
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monocyte-macrophage differentiation antigen
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Green Fluorescent Proteins
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sphingosine 1-phosphate
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Phosphatidate Phosphatase
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Plpp3 protein, mouse
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Sphingosine