Sphingosine kinase 1 mediation of expression of the anaphylatoxin receptor C5L2 dampens the inflammatory response to endotoxin.

PloS One
Kurt BachmaierAsrar B Malik

Abstract

The complement anaphylatoxin C5a has a pathogenetic role in endotoxin-induced lung inflammatory injury by regulating phagocytic cell migration and activation. Endotoxin and C5a activate the enzyme sphingosine kinase (Sphk) 1 to generate the signaling lipid sphingosine-1-phosphate (S1P), a critical regulator of phagocyte function. We assessed the function of Sphk1 and S1P in experimental lung inflammatory injury and determined their roles in anaphylatoxin receptor signaling and on the expression of the two C5a receptors, C5aR (CD88) and C5L2, on phagocytes. We report that Sphk1 gene deficient (Sphk1(-/-)) mice had augmented lung inflammatory response to endotoxin compared to wild type mice. Sphk1 was required for C5a-mediated reduction in cytokine and chemokine production by macrophages. Moreover, neutrophils from Sphk1(-/-) mice failed to upregulate the anaphylatoxin receptor C5L2 in response to LPS. Exogenous S1P restored C5L2 cell surface expression of Sphk1(-/-) mouse neutrophils to wild type levels but had no effect on cell surface expression of the other anaphylatoxin receptor, CD88. These results provide the first genetic evidence of the crucial role of Sphk1 in regulating the balance between expression of CD88 and C5L2 i...Continue Reading

References

Jul 8, 1999·Nature Medicine·B J CzermakP A Ward
Feb 19, 2002·Kidney International·Mary C PerianayagamBertrand L Jaber
Jul 3, 2002·The Journal of Clinical Investigation·Niels C RiedemannPeter A Ward
Aug 23, 2003·Immunity·Niels C RiedemannPeter A Ward
Sep 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Glenn DorsamEdward J Goetzl
Dec 23, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Niels C RiedemannPeter A Ward
Mar 17, 2004·American Journal of Respiratory and Critical Care Medicine·Xinqi PengJoe G N Garcia
Jul 30, 2004·American Journal of Respiratory and Critical Care Medicine·Bryan J McVerryJoe G N Garcia
Aug 11, 2004·The Journal of Biological Chemistry·Farazeela Bte Mohd IbrahimAlirio J Melendez
Oct 2, 2004·The Journal of Biological Chemistry·Maria L AllendeRichard L Proia
Jan 7, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Markus Huber-LangPeter A Ward
Apr 23, 2005·Immunity·Heiko HawlischJörg Köhl
Jul 7, 2005·Nature Reviews. Immunology·Hugh Rosen, Edward J Goetzl
Oct 6, 2005·The Journal of Biological Chemistry·Norma P GerardCraig Gerard
Nov 30, 2005·Molecular and Cellular Biology·Kiyomi MizugishiRichard L Proia
Jan 26, 2006·Blood·Eric CamererShaun R Coughlin
Dec 1, 2006·The Journal of Biological Chemistry·Sarah Spiegel, Sheldon Milstien
Jan 12, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Petra HänelMarkus H Gräler
Apr 14, 2007·Current Drug Targets·J R Jacobson, J G N Garcia
Dec 26, 2007·Critical Care Medicine·R Phillip DellingerUNKNOWN World Federation of Societies of Intensive and Critical Care Medicine
Jan 30, 2008·Immunology and Cell Biology·Hyun LeeCharles R Mackay
Mar 1, 2008·The International Journal of Biochemistry & Cell Biology·Peter N PushparajAlirio J Melendez
May 6, 2008·Nature Medicine·Daniel RittirschPeter A Ward
Jul 1, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Michael A FlierlPeter A Ward
Aug 5, 2008·Biochimica Et Biophysica Acta·Timothy HlaJason Michaud
Mar 20, 2010·The Journal of Biological Chemistry·Anke DiAsrar B Malik
Jul 2, 2010·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Liyan WangYan Li
Aug 20, 2010·Nature Immunology·Daniel RicklinJohn D Lambris

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Citations

Jan 15, 2013·Journal of Allergy·Wai Y Sun, Claudine S Bonder
Mar 2, 2013·American Journal of Respiratory Cell and Molecular Biology·Viswanathan NatarajanJoe G N Garcia
May 9, 2013·Current Opinion in Lipidology·Christina Christoffersen, Lars Bo Nielsen
May 29, 2012·Advanced Drug Delivery Reviews·S Moein MoghimiA Christy Hunter
Dec 15, 2015·Journal of Molecular and Cellular Cardiology·Hicham LabaziS Jamal Mustafa
Apr 11, 2015·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·Zeynab KolahdoozLeila Dargahi
Mar 21, 2017·Nature Reviews. Nephrology·Min ChenMing-Hui Zhao
Dec 6, 2016·Molecular Immunology·Yves LaumonnierChristian Karsten
Sep 26, 2014·The Journal of Biological Chemistry·Wenliang ZhangMenq-Jer Lee
Dec 15, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rui LiTrent M Woodruff
Jul 3, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xaria X LiTrent M Woodruff
Jul 15, 2017·Journal of Immunology Research·Ting ZhangKe Li
Feb 17, 2017·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Xiao-Jing SunMing-Hui Zhao
Feb 14, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Divya A VerghesePeter S Heeger
Jun 5, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xaria X LiTrent M Woodruff
Sep 26, 2020·Medicina·Rόisín C ThomasCordula M Stover

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Methods Mentioned

BETA
ELISA
flow cytometry
Assay

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