title: Platelet and Erythrocyte Sources of S1P Are Redundant for Vascular Development and Homeostasis, but Both Rendered Essential After Plasma S1P Depletion in Anaphylactic Shock.
abstract: BACKGROUND
  Sphingosine-1-phosphate (S1P) signaling is essential for vascular development and postnatal vascular homeostasis. The relative importance of S1P sources sustaining these processes remains unclear.
  
  
  OBJECTIVE
  To address the level of redundancy in bioactive S1P provision to the developing and mature vasculature.
  
  
  RESULTS
  S1P production was selectively impaired in mouse platelets, erythrocytes, endothelium, or smooth muscle cells by targeted deletion of genes encoding sphingosine kinases -1 and -2. S1P deficiency impaired aggregation and spreading of washed platelets and profoundly reduced their capacity to promote endothelial barrier function ex vivo. However, and in contrast to recent reports, neither platelets nor any other source of S1P was essential for vascular development, vascular integrity, or hemostasis/thrombosis. Yet rapid and profound depletion of plasma S1P during systemic anaphylaxis rendered both platelet- and erythrocyte-derived S1P essential for survival, with a contribution from blood endothelium observed only in the absence of circulating sources. Recovery was sensitive to aspirin in mice with but not without platelet S1P, suggesting that platelet activation and stimulus-response coupling is needed. S1P deficiency aggravated vasoplegia in this model, arguing a vital role for S1P in maintaining vascular resistance during recovery from circulatory shock. Accordingly, the S1P2 receptor mediated most of the survival benefit of S1P, whereas the endothelial S1P1 receptor was dispensable for survival despite its importance for maintaining vascular integrity.
  
  
  CONCLUSIONS
  Although source redundancy normally secures essential S1P signaling in developing and mature blood vessels, profound depletion of plasma S1P renders both erythrocyte and platelet S1P pools necessary for recovery and high basal plasma S1P levels protective during anaphylactic shock.
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Salomé L
authors: SL
authors: Gazit
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Boubacar
authors: B
authors: Mariko
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Patrice
authors: P
authors: Thérond
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Benoit
authors: B
authors: Decouture
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Yuquan
authors: Y
authors: Xiong
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Ludovic
authors: L
authors: Couty
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Philippe
authors: P
authors: Bonnin
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Véronique
authors: V
authors: Baudrie
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Sylvain M
authors: SM
authors: Le Gall
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Blandine
authors: B
authors: Dizier
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Nesrine
authors: N
authors: Zoghdani
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Jessica
authors: J
authors: Ransinan
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Justin R
authors: JR
authors: Hamilton
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Pascale
authors: P
authors: Gaussem
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Pierre-Louis
authors: PL
authors: Tharaux
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Jerold
authors: J
authors: Chun
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Shaun R
authors: SR
authors: Coughlin
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Christilla
authors: C
authors: Bachelot-Loza
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Timothy
authors: T
authors: Hla
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.).
authors: Benoit
authors: B
authors: Ho-Tin-Noé
authors: From the INSERM U970, Paris Cardiovascular Research Centre, 75015 Paris, France (S.L.G., B.M., L.C., V.B., S.M.L.G., N.Z., J.R., P.-L.T., E.C.); Université Sorbonne Paris Cité, Paris, France (S.L.G., B.M., B. Decouture, L.C., P.B., V.B., S.M.L.G., B. Dizier, N.Z., J.R., P.G., P.-L.T., C.B.-L., B.H.-T.-N., E.C.); AP-HP, Hôpital Bicêtre, Service de Biochimie, 94275 Le Kremlin Bicêtre, France (P.T.); Lip(Sys)2-Biochimie appliquée, Université Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France (P.T.); INSERM U1140, Faculté de Pharmacie, 75006 Paris, France (B. Decouture, B. Dizier, P.G., C.B.-L.); Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York (Y.X., T.H.); AP-HP, Hôpital Lariboisière, Physiologie Clinique-Explorations-Fonctionnelles, INSERM U965, 75010, Paris, France (P.B.); Australian Centre for Blood Diseases & Department of Clinical Haematology, Monash University, Melbourne, Australia (J.R.H.); AP-HP, Hôpital Européen Georges Pompidou, Service d'Hématologie Biologique, Paris, France (P.G.); Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA (J.C.); Cardiovascular Research Institute, University of California, San Francisco (S.R.C.); and INSERM U698, 75018 Paris, France (B.H.-T.-N.). eric.camerer@inserm.fr.
authors: Eric
authors: E
authors: Camerer
mesh_terms: D000707:Anaphylaxis / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D001808:Blood Vessels / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D004912:Erythrocytes / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids / Q000172:deficiency*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000172:deficiency
chemical_list: D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: anaphylaxis; endothelium; shock; sphingosine-1-phosphate; vascular endothelial function; vascular permeability; vascular tone regulation