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- Title
Lymphatic endothelial cell sphingosine kinase activity is required for lymphocyte egress and lymphatic patterning.
- Authors
Pham, Trung H M; Baluk, Peter; Xu, Ying; Grigorova, Irina; Bankovich, Alex J; Pappu, Rajita; Coughlin, Shaun R; McDonald, Donald M; Schwab, Susan R; Cyster, Jason G
- Abstract
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.
- Publication
The Journal of experimental medicine, 2010, Vol 207, Issue 1, p17
- ISSN
1540-9538
- Publication type
Journal Article
- DOI
10.1084/jem.20091619