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Lymphatic endothelial cell sphingosine kinase activity is required for lymphocyte egress and lymphatic patterning.

http://www.ncbi.nlm.nih.gov/pubmed/20026661

Lymphocyte egress from lymph nodes (LNs) is dependent on sphingosine-1-phosphate (S1P), but the cellular source of this S1P is not defined. We generated mice that expressed Cre from the lymphatic vessel endothelial hyaluronan receptor 1 (Lyve-1) locus and that showed efficient recombination of loxP-flanked genes in lymphatic endothelium. We report that mice with Lyve-1 CRE-mediated ablation of sphingosine kinase (Sphk) 1 and lacking Sphk2 have a loss of S1P in lymph while maintaining normal plasma S1P. In Lyve-1 Cre+ Sphk-deficient mice, lymphocyte egress from LNs and Peyer's patches is blocked. Treatment with pertussis toxin to overcome Galphai-mediated retention signals restores lymphocyte egress. Furthermore, in the absence of lymphatic Sphks, the initial lymphatic vessels in nonlymphoid tissues show an irregular morphology and a less organized vascular endothelial cadherin distribution at cell-cell junctions. Our data provide evidence that lymphatic endothelial cells are an in vivo source of S1P required for lymphocyte egress from LNs and Peyer's patches, and suggest a role for S1P in lymphatic vessel maturation.

Pubmed ID: 20026661 RIS Download

Mesh terms: Animals | Cell Movement | Endothelial Cells | GTP-Binding Protein alpha Subunits, Gi-Go | Glycoproteins | Intercellular Junctions | Lymph Nodes | Lymphocytes | Lysophospholipids | Mice | Mice, Knockout | Pertussis Toxin | Peyer's Patches | Phosphotransferases (Alcohol Group Acceptor) | Signal Transduction | Sphingosine

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Associated grants

  • Agency: NHLBI NIH HHS, Id: P01 HL024136
  • Agency: NHLBI NIH HHS, Id: R01 HL059157
  • Agency: NHLBI NIH HHS, Id: R01 HL065590
  • Agency: Howard Hughes Medical Institute, Id:

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