Publication Date:
2002-03-30
Description:
Blood lymphocyte numbers, essential for the development of efficient immune responses, are maintained by recirculation through secondary lymphoid organs. We show that lymphocyte trafficking is altered by the lysophospholipid sphingosine-1-phosphate (S1P) and by a phosphoryl metabolite of the immunosuppressive agent FTY720. Both species were high-affinity agonists of at least four of the five S1P receptors. These agonists produce lymphopenia in blood and thoracic duct lymph by sequestration of lymphocytes in lymph nodes, but not spleen. S1P receptor agonists induced emptying of lymphoid sinuses by retention of lymphocytes on the abluminal side of sinus-lining endothelium and inhibition of egress into lymph. Inhibition of lymphocyte recirculation by activation of S1P receptors may result in therapeutically useful immunosuppression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mandala, Suzanne -- Hajdu, Richard -- Bergstrom, James -- Quackenbush, Elizabeth -- Xie, Jenny -- Milligan, James -- Thornton, Rosemary -- Shei, Gan-Ju -- Card, Deborah -- Keohane, CarolAnn -- Rosenbach, Mark -- Hale, Jeffrey -- Lynch, Christopher L -- Rupprecht, Kathleen -- Parsons, William -- Rosen, Hugh -- New York, N.Y. -- Science. 2002 Apr 12;296(5566):346-9. Epub 2002 Mar 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Rheumatology, Merck Research Laboratories, Post Office Box 2000, Rahway, NJ 07065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11923495" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
B-Lymphocytes/drug effects/*physiology
;
Binding, Competitive
;
CHO Cells
;
Calcium/metabolism
;
Cricetinae
;
Cyclic AMP/metabolism
;
Fingolimod Hydrochloride
;
Guanosine 5'-O-(3-Thiotriphosphate)/metabolism
;
Humans
;
Immunosuppressive Agents/metabolism/pharmacology
;
Ligands
;
Lymph Nodes/cytology/drug effects
;
Lymphocyte Count
;
Lymphopenia/chemically induced
;
*Lysophospholipids
;
Mice
;
Organophosphates/chemical synthesis/chemistry/metabolism/*pharmacology
;
Organophosphonates/chemical synthesis/chemistry/metabolism/*pharmacology
;
Phosphorylation
;
Propylene Glycols/*metabolism/pharmacology
;
Rats
;
Receptors, Cell Surface/*agonists/metabolism
;
*Receptors, G-Protein-Coupled
;
Receptors, Lysophospholipid
;
Sphingosine/*analogs & derivatives/metabolism/*pharmacology
;
Spleen/cytology/drug effects
;
Stereoisomerism
;
T-Lymphocytes/drug effects/*physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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