title: Sphingosine kinase 1 and sphingosine-1-phosphate receptor 2 are vital to recovery from anaphylactic shock in mice.
abstract: Sphingosine kinase 1 (SphK1) and SphK2 are ubiquitous enzymes that generate sphingosine-1-phosphate (S1P), a ligand for a family of G protein-coupled receptors (S1PR1-S1PR5) with important functions in the vascular and immune systems. Here we explore the role of these kinases and receptors in recovery from anaphylaxis in mice. We found that Sphk2-/- mice had a rapid recovery from anaphylaxis. In contrast, Sphk1-/- mice showed poor recovery from anaphylaxis and delayed histamine clearance. Injection of S1P into Sphk1-/- mice increased histamine clearance and promoted recovery from anaphylaxis. Adoptive cell transfer experiments demonstrated that SphK1 activity was required in both the hematopoietic and nonhematopoietic compartments for recovery from anaphylaxis. Mice lacking the S1P receptor S1PR2 also showed a delay in plasma histamine clearance and a poor recovery from anaphylaxis. However, S1P did not promote the recovery of S1pr2-/- mice from anaphylaxis, whereas S1pr2+/- mice showed partial recovery. Unlike Sphk2-/- mice, Sphk1-/- and S1pr2-/- mice had severe hypotension during anaphylaxis. Thus, SphK1-produced S1P regulates blood pressure, histamine clearance, and recovery from anaphylaxis in a manner that involves S1PR2. This suggests that specific S1PR2 agonists may serve to counteract the vasodilation associated with anaphylactic shock.
authors.affiliation: Laboratory of Molecular Immunogenetics, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Olivera
authors.forename: Christoph
authors.initials: C
authors.lastname: Eisner
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Sandra
authors.initials: S
authors.lastname: Dillahunt
authors.forename: Laura
authors.initials: L
authors.lastname: Allende
authors.forename: Galina
authors.initials: G
authors.lastname: Tuymetova
authors.forename: Wendy
authors.initials: W
authors.lastname: Watford
authors.forename: Francoise
authors.initials: F
authors.lastname: Meylan
authors.forename: Susanne C
authors.initials: SC
authors.lastname: Diesner
authors.forename: Lingli
authors.initials: L
authors.lastname: Li
authors.forename: Jurgen
authors.initials: J
authors.lastname: Schnermann
authors.forename: Richard L
authors.initials: RL
authors.lastname: Proia
authors.forename: Juan
authors.initials: J
authors.lastname: Rivera
mesh_terms: D000707:Anaphylaxis / Q000201:enzymology*; D000818:Animals; D016026:Bone Marrow Transplantation; D015971:Gene Expression Regulation, Enzymologic; D005919:Glomerular Filtration Rate; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D010539:Permeability; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D000099157:Sphingosine Kinase
chemical_list: D006632:Histamine; D017853:Phosphotransferases (Alcohol Group Acceptor); D049349:Receptors, Lysosphingolipid; D000099157:Sphingosine Kinase
references.citation: Mol Cell Biol. 2004 Oct;24(19):8765-77
references.pmid: 15367693
references.citation: Microvasc Res. 1995 Nov;50(3):323-37
references.pmid: 8583948
references.citation: J Clin Invest. 1997 Mar 1;99(5):901-14
references.pmid: 9062348
references.citation: Chem Immunol Allergy. 2008;94:67-82
references.pmid: 18802338
references.citation: Cardiovasc Res. 2003 Apr 1;58(1):170-7
references.pmid: 12667959
references.citation: FASEB J. 2001 May;15(7):1212-4
references.pmid: 11344091
references.citation: J Clin Invest. 1997 Mar 1;99(5):915-25
references.pmid: 9062349
references.citation: FASEB J. 2005 Oct;19(12):1646-56
references.pmid: 16195373
references.citation: J Exp Med. 1999 Jul 5;190(1):1-8
references.pmid: 10429665
references.citation: Am J Respir Crit Care Med. 1999 Oct;160(4):1142-9
references.pmid: 10508800
references.citation: Biochim Biophys Acta. 2006 Mar;1761(3):367-76
references.pmid: 16571380
references.citation: Clin Exp Allergy. 2000 Aug;30(8):1144-50
references.pmid: 10931122
references.citation: J Clin Invest. 2006 Nov;116(11):2935-44
references.pmid: 17080194
references.citation: Ann Allergy Asthma Immunol. 2006 Nov;97(5):596-602
references.pmid: 17165265
references.citation: Cell Biol Int. 2009 Apr;33(4):534-41
references.pmid: 19230848
references.citation: Cardiovasc Res. 2009 May 1;82(2):212-20
references.pmid: 19233865
references.citation: J Clin Invest. 2009 Jul;119(7):1871-9
references.pmid: 19603543
references.citation: Cardiovasc Res. 2009 May 1;82(2):221-8
references.pmid: 19287048
references.citation: J Allergy Clin Immunol. 2003 Oct;112(4 Suppl):S53-9
references.pmid: 14530789
references.citation: Mol Immunol. 2002 Sep;38(16-18):1239-45
references.pmid: 12217390
references.citation: J Allergy Clin Immunol. 2002 Aug;110(2):298-303
references.pmid: 12170272
references.citation: J Allergy Clin Immunol. 2008 Feb;121(2 Suppl):S402-7; quiz S420
references.pmid: 18241691
references.citation: FASEB J. 2009 Oct;23(10):3506-15
references.pmid: 19535686
references.citation: J Physiol. 1959 Oct;147:437-49
references.pmid: 14399150
references.citation: Scand J Clin Lab Invest. 2001;61(6):449-52
references.pmid: 11681534
references.citation: Anal Biochem. 2009 Feb 1;385(1):34-41
references.pmid: 19026982
references.citation: Kidney Int. 1984 Aug;26(2):144-52
references.pmid: 6094908
references.citation: Circ Res. 2008 Aug 1;103(3):315-24
references.pmid: 18583713
references.citation: N Engl J Med. 1991 Mar 14;324(11):716-20
references.pmid: 1997836
references.citation: J Biol Chem. 2006 Feb 3;281(5):2515-25
references.pmid: 16316995
references.citation: Agents Actions. 1991 Jul;33(3-4):349-58
references.pmid: 1683106
references.citation: J Pharmacol Exp Ther. 2004 May;309(2):758-68
references.pmid: 14747617
references.citation: Nat Rev Immunol. 2008 Oct;8(10):753-63
references.pmid: 18787560
references.citation: Neuroscience. 1983 Aug;9(4):721-39
references.pmid: 6312374
references.citation: Novartis Found Symp. 2004;257:1-5
references.pmid: 15025388
references.citation: J Biol Chem. 2004 Dec 10;279(50):52487-92
references.pmid: 15459201
references.citation: Am J Physiol Regul Integr Comp Physiol. 2007 Jan;292(1):R440-6
references.pmid: 16990495
references.citation: FASEB J. 2008 Jan;22(1):307-15
references.pmid: 17785606
references.citation: Circulation. 2003 Jul 22;108(3):342-7
references.pmid: 12847068
references.citation: Nature. 1996 Apr 18;380(6575):634-6
references.pmid: 8602265
references.citation: Trends Immunol. 2004 May;25(5):266-73
references.pmid: 15099567
references.citation: Circ Res. 2008 Mar 28;102(6):669-76
references.pmid: 18258856
references.citation: Res Exp Med (Berl). 1990;190(4):239-52
references.pmid: 2218074
references.citation: Br J Pharmacol. 2009 May;157(1):24-33
references.pmid: 19309354
references.citation: Immunity. 2007 Mar;26(3):287-97
references.pmid: 17346996
references.citation: Allergy. 2009 Feb;64(2):204-12
references.pmid: 19178399
references.citation: Mol Cell Biol. 2005 Dec;25(24):11113-21
references.pmid: 16314531
references.citation: J Exp Med. 2004 Apr 5;199(7):959-70
references.pmid: 15067032
references.citation: Arterioscler Thromb Vasc Biol. 2007 Jun;27(6):1312-8
references.pmid: 17431187
references.citation: Chem Immunol Allergy. 2005;85:185-204
references.pmid: 15970658
references.citation: Am J Physiol Renal Physiol. 2004 Mar;286(3):F590-6
references.pmid: 14600035
references.citation: Am J Clin Nutr. 2007 May;85(5):1185-96
references.pmid: 17490952
references.citation: J Biol Chem. 2007 Apr 6;282(14):10690-6
references.pmid: 17284444
references.citation: J Biol Chem. 2004 Jul 9;279(28):29367-73
references.pmid: 15138255
references.citation: Clin Exp Immunol. 2008 Jul;153(1):1-9
references.pmid: 18577027
references.citation: J Biol Chem. 2005 Mar 18;280(11):9833-41
references.pmid: 15590668
references.citation: Circ Res. 2008 Nov 7;103(10):1164-72
references.pmid: 18849324
references.citation: Am J Physiol Heart Circ Physiol. 2009 Jan;296(1):H33-42
references.pmid: 19011048
references.citation: Cardiovasc Res. 2009 May 1;82(2):193-200
references.pmid: 19282351
references.citation: Kidney Int. 1983 Oct;24(4):534-41
references.pmid: 6417393
references.citation: FASEB J. 2006 Apr;20(6):702-4
references.pmid: 16476702