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Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo
Abstract
Sphingosine 1-phosphate (S1P, 1) regulates vascular barrier and lymphoid development, as well as lymphocyte egress from lymphoid organs, by activating high-affinity S1P1 receptors. We used reversible chemical probes (i) to gain mechanistic insights into S1P systems organization not accessible through genetic manipulations and (ii) to investigate their potential for therapeutic modulation. Vascular (but not airway) administration of the preferred R enantiomer of an in vivo-active chiral S1P1 receptor antagonist induced loss of capillary integrity in mouse skin and lung. In contrast, the antagonist did not affect the number of constitutive blood lymphocytes. Instead, alteration of lymphocyte trafficking and phenotype required supraphysiological elevation of S1P1 tone and was reversed by the antagonist. In vivo two-photon imaging of lymph nodes confirmed requirements for obligate agonism, and the data were consistent with the presence of a stromal barrier mechanism for gating lymphocyte egress. Thus, chemical modulation reveals differences in S1P-S1P1 'set points' among tissues and highlights both mechanistic advantages (lymphocyte sequestration) and risks (pulmonary edema) of therapeutic intervention.
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“The stereoselective engagement of protein targets is a feature of numerous chemical probes and drugs15–19”
From Expedited mapping of the ligandable proteome using fully functionalized enantiomeric probe pairs (2019) · cites this paper as [19]
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“, 2005); and (iii) the finding that novel direct competitive S1P1 antagonists did not block lymphocyte egress in vivo (Sanna et al., 2006).”
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InfluentialSphingosine 1-Phosphate Receptor Signaling
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Self-citationPersistent signaling induced by FTY720-phosphate is mediated by internalized S1P1 receptors
Müllershausen, F., Zécri, F. J., Cetin, C., Billich, A., Guerini, D., & Seuwen, K. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.173 · Cited by 382
“The concept of endothelial cells as 'gatekeepers' for lymphocyte egress was corroborated in a study showing that an S1P1-selective antagonist not only failed to induce lymphopenia, but even enhanced vascular leakag”
Camerer, E., Regard, J. B., Cornelissen, I., Srinivasan, Y., Duong, D. N., Palmer, D., Pham, T. H. M., Wong, J. S., Pappu, R., & Coughlin, S. R. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38575 · Cited by 367
Erythrocytes store and release sphingosine 1‐phosphate in blood
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“Another strong argument is that so far only S1P1 receptor agonists but not antagonists induce lymphopenia in rodents (6, 16, 17).”
BackgroundExtracellular and Intracellular Actions of Sphingosine-1-Phosphate
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“Administration of one class of pharmacological antagonists of S1P 1 led to marked increases in basal permeability of the mouse lung (Foss et al., 2006; Sanna et al., 2006).”
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Kihara, Y., Maceyka, M. W., Spiegel, S., & Chun, J. J. M. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12678 · Cited by 339
“…N/A N/A N/A GTPγS Gonzalez-Cabrera et al., 2008 CYM-5442 EC50 1.2 N/A N/A N/A N/A GTPγS Gonzalez-Cabrera et al., 2008 W146 EC50 (Ki) 398 (77) N/A N/A N/A N/A GTPγS Sanna et al., 2006 NIBR-0213 (Ki) (2) N/A N/A N/A N/A GTPγS Quancard et al., 2012 VPC03090-P EC50 (Ki) (21–24) N/A (51–58.7) 17.7b…”
InfluentialGaengel, K., Niaudet, C., Hagikura, K., Laviña, B., Muhl, L., Hofmann, J. J., Ebarasi, L., Nyström, S., Rymo, S., Chen, L. L., et al. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.08.005 · Cited by 326
“In agreement with the gene knockout data, systemic administration of the S1PR1-specific antagonist (R)-W146 (Sanna et al., 2006) to newborn mice resulted in endothelial hypersprouting in the postnatal retina (Figure 3A).”
ResultCahalan, M. D., & Parker, I. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.24.021605.090620 · Cited by 303
Self-citationPassing the Vascular Barrier: Endothelial Signaling Processes Controlling Extravasation
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Sphingosine-1-phosphate protects endothelial glycocalyx by inhibiting syndecan-1 shedding
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“W146 is a S1P1 receptor selective antagonist (11, 27).”
BackgroundTherapeutic opportunities for manipulating TReg cells in autoimmunity and cancer
von Boehmer, H., & Daniel, C. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3683 · Cited by 230
Sphingosine-1-Phosphate and Its Receptors: Structure, Signaling, and Influence
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“On the contrary, application of a S1P1 receptor antagonist (W146), induced loss of capillary integrity in mouse skin and lung (Sanna et al., 2006), and the most recently developed potent S1P1 selective antagonist NIBR-0213 induced transient lung and heart permeability defects in rats, which…”
Functions of the Multifaceted Family of Sphingosine Kinases and Some Close Relatives
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Engagement of S1P1-degradative mechanisms leads to vascular leak in mice
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“It is also known that S1P1 action is essential for adherens junction assembly (28) and inhibition of pathologic vascular permeability both in vitro (29) and in vivo (13, 30).”
BackgroundCardiac and vascular effects of fingolimod: Mechanistic basis and clinical implications
Camm, A. J., Hla, T., Bakshi, R., & Brinkmann, V. (2014) · American Heart Journal · doi:10.1016/j.ahj.2014.06.028 · Cited by 213
Fingolimod phosphate promotes the neuroprotective effects of microglia
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“We then blocked FTY720 binding to each S1P receptor subtype using selective antagonists for S1P 1 (W146), S1P 3 /S1P 5 (suramin), and S1P 4 (CYM50358).”
InfluentialFingolimod-associated macular edema
Jain, N., & Bhatti, M. T. (2012) · Neurology · doi:10.1212/wnl.0b013e318248deea · Cited by 201
Cortical sinus probing, S1P1-dependent entry and flow-based capture of egressing T cells
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The vascular S1P gradient—Cellular sources and biological significance
Hla, T. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2008.07.003 · Cited by 188
“Treatment with S1P1 antagonists induced spontaneous permeability in the mouse lung, suggesting that tonic signaling of S1P1 under physiological conditions is important in maintaining basal lung vascular permeability [81].”
BackgroundSphingosine-1-phosphate and immune regulation: trafficking and beyond
Chi, H. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.11.002 · Cited by 184
Expedited mapping of the ligandable proteome using fully functionalized enantiomeric probe pairs
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Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation
Zhang, G., Yang, L., Kim, G. S., Ryan, K. P., Lu, S., O’Donnell, R. K., Spokes, K., Shapiro, N. I., Aird, W. C., Kluk, M., et al. (2013) · Blood · doi:10.1182/blood-2012-11-467191 · Cited by 175
“This pathway is essential for vascular stabilization(7) and inhibition of vascular permeability.(8,9) In sharp contrast, we recently found that S1PR2 antagonizes S1PR1-Gi-PI3K signaling in the endothelium through activation of the G12/13-Rho-Rho kinase (ROCK)-PTEN pathway.”
Sphingosine 1-phosphate in coagulation and inflammation
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“Administration of S1P or S1P1 selective agonist shows protective effects in rodent models of lipopolysaccharide (LPS)-induced lung injury and vascular permeability [134, 135], VEGF-induced vascular leakage [102], and anaphylaxis challenges [65], while administration of S1P1 antagonists induces a loss of capillary inte…”
A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis
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“W146 maintains an adequate in vivo receptor blockade for only 5–6 h (Sanna et al., 2006), and shedding reoccurred 6 h after a single dose of W146, suggesting that S1pr1 inhibition does not affect the viability of MKs (Fig.”
BackgroundExit Strategies: S1P Signaling and T Cell Migration
Baeyens, A., Fang, V., Chen, C., & Schwab, S. R. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.10.005 · Cited by 174
“The latter possibility is consistent with two additional findings suggesting that endothelial S1PR1, unlike S1PR1 on T cells in blood, is not saturated in homeostasis: the observation that S1PR1 agonists alter endothelial permeability in vivo, and that inflammation increases endothelial S1PR1 signaling [88,89].”
ResultAdvancing Biological Understanding and Therapeutics Discovery with Small-Molecule Probes
Schreiber, S. L., Kotz, J., Li, M., Aubé, J., Austin, C. P., Reed, J. C., Rosen, H., White, E. L., Sklar, L. A., Lindsley, C. W., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.023 · Cited by 173
“3) with in vivo activity was developed through rational synthesis and used to explore the impact of perturbing this receptor on lymphocyte movement and function, providing evidence that the therapeutic effects of FTY720 are primarily mediated through this receptor (Sanna et al. , 2006).”
Self-citationThe emerging role of FTY720 (Fingolimod) in cancer treatment
White, C., Alshaker, H. A., Cooper, C., Winkler, M. H., & Pchejetski, D. (2016) · Oncotarget · doi:10.18632/oncotarget.7145 · Cited by 175
“FTY720-p is an agonist of S1Prs 1, 3, 4 and 5 and same time a functional antagonist of S1PR1 receptor [124, 129].”
BackgroundChemical modulators of sphingosine-1-phosphate receptors as barrier-oriented therapeutic molecules
Marsolais, D., & Rosen, H. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2356 · Cited by 169
Self-citationUhlig, S., & Gulbins, E. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200804-595so · Cited by 161
“, W146 blocks S1P1 receptors [65] and JTE 013 S1P2 receptors [66]).”
BackgroundJanes, K., Little, J. W., Li, C., Bryant, L., Chen, C., Chen, Z., Kamocki, K., Doyle, T. M., Snider, A. J., Esposito, E., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.569574 · Cited by 157
“2 nmol/day) (52), in rats with previously implanted i.”
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“In the immune system, changes in local S1P concentration and gradient can alter inflammatory cell responses [22,23], affect the barrier function of endothelial cells [24–26], and modify lymphocyte migration patterns [15,16,27–29].”
BackgroundResultFoss, F. W., Snyder, A. H., Davis, M. D., Rouse, M. D., Okusa, M. D., Lynch, K. R., & Macdonald, T. L. (2006) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2006.10.060 · Cited by 160
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Tipping the gatekeeper: S1P regulation of endothelial barrier function
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“It is currently controversial whether pharmacological compounds blocking or stimulating S1P1 signaling act mainly on lymphocytes or lymphatic endothelial cells, as S1P1 expressed on lymphatic endothelium may participate in lymphocyte exit control through regulation of endothelial barrier properties (40, 53, 54).”
BackgroundFeng, H., Stachura, D. L., White, R. M., Gutiérrez, A., Zhang, L., Sanda, T., Jette, C. A., Testa, J. R., Neuberg, D. S., Langenau, D. M., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.09.009 · Cited by 150
“…the ligand-binding domain of zebrafish s1p1 is also highly conserved, we tested whether the S1P1 pathway regulated the cellular aggregation phenotype of zebrafish Myc;Cre;bcl-2 T-LBL cells, using W146, a specific S1P1 antagonist (Sanna et al., 2006), to treat malignant cells from transgenic fish.”
BackgroundInsights into the pharmacological relevance of lysophospholipid receptors
Mutoh, T., Rivera, R. R., & Chun, J. J. M. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01622.x · Cited by 137
“An S1P1-specific antagonist called W146 can induce loss of capillary integrity (Sanna et al., 2006).”
BackgroundThe structure and function of the S1P1 receptor
O'Sullivan, C., & Dev, K. K. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.05.002 · Cited by 138
Yoon, C. M., Hong, B. S., Moon, H. G., Lim, S., Suh, P., Kim, Y., Chae, C., & Gho, Y. S. (2008) · Blood · doi:10.1182/blood-2007-11-125203 · Cited by 134
Sphingosine-1-phosphate receptor 1 activation in astrocytes contributes to neuropathic pain
Chen, Z., Doyle, T. M., Luongo, L., Largent‐Milnes, T. M., Giancotti, L. A., Kolar, G. R., Squillace, S., Boccella, S., Walker, J. K., Pendleton, A. L., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1820466116 · Cited by 130
“Similar past discrepancies in pharmacological outcomes between systemic administration of FTY720 and W146 led to the conclusion that FTY720 did not act as a functional S1PR1 antagonist (46).”
ResultA Potent and Selective S1P1 Antagonist with Efficacy in Experimental Autoimmune Encephalomyelitis
Quancard, J., Bollbuck, B., Janser, P., Angst, D., Berst, F., Buehlmayer, P., Streiff, M. B., Beerli, C., Brinkmann, V., Guerini, D., et al. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.07.016 · Cited by 128
Second generation S1P pathway modulators: Research strategies and clinical developments
Bigaud, M., Guerini, D., Billich, A., Bassilana, F., & Brinkmann, V. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.11.001 · Cited by 129
“Endothelial cells Angiogenesis S1P1 [135] [136] Barrier enhancement S1P1 [68][137][69] Barrier decrease S1P3 [68][137] Vasodilation, eNOS activation S1P3, S1P1 [74][70] [75][138] Heart atrial myocytes Heart rate reduction S1P3, S1P1 [56][62][55] [200]”
BackgroundInfluentialGonzalez‐Cabrera, P. J., Jo, E., Sanna, M., Brown, S. J., Leaf, N. B., Marsolais, D., Schaeffer, M., Chapman, J. V., Cameron, M. D., Guerrero, M., et al. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.049783 · Cited by 129
“We have data indicating that endothelial integrity is tonically regulated by the S1P-S1P1 axis (Sanna et al., 2006).”
BackgroundInfluentialSelf-citationIkeda, H., Watanabe, N., Ishii, I., Shimosawa, T., Kume, Y., Tomiya, T., Inoue, Y., Nishikawa, T., Ohtomo, N., Tanoue, Y., et al. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m800496-jlr200 · Cited by 125
Finding a way out: S1P signaling and immune cell migration
Baeyens, A. A. L., & Schwab, S. R. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-081519-083952 · Cited by 123
Tran, J. Q., Hartung, J. P., Peach, R., Boehm, M. F., Rosen, H., Smith, H., Brooks, J. L., Timony, G. A., Olson, A. D., Gujrathi, S., et al. (2017) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.887 · Cited by 113
Self-citationPhosphorylated FTY720 stimulates ERK phosphorylation in astrocytes via S1P receptors
Osinde, M., Müllershausen, F., & Dev, K. K. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.11.010 · Cited by 112
Oskeritzian, C. A., Price, M. M., Hait, N. C., Kapitonov, D., Falanga, Y. T., Morales, J. K., Ryan, J. J., Milstien, S., & Spiegel, S. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20091513 · Cited by 112
“Conversely, treatment with the S1P1 antagonist W146 caused pulmonary edema (Sanna et al., 2006).”
Vascular and immunobiology of the circulatory sphingosine 1-phosphate gradient
Yanagida, K., & Hla, T. (2017) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021014-071635 · Cited by 109
GPCR crystal structures: Medicinal chemistry in the pocket
Shonberg, J., Kling, R. C., Gmeiner, P., & Löber, S. (2014) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2014.12.034 · Cited by 118
Gossens, K., Naus, S., Corbel, S. Y., Lin, S., Rossi, F. M. V., Kast, J., & Ziltener, H. J. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20082502 · Cited by 108
FOXF1 maintains endothelial barrier function and prevents edema after lung injury
Cai, Y., Bolte, C., Le, T. T., Goda, C., Xu, Y. J., Kalin, T. V., & Kalinichenko, V. V. (2016) · Science Signaling · doi:10.1126/scisignal.aad1899 · Cited by 107
Adachi, K., & Chiba, K. (2007) · Perspectives in Medicinal Chemistry · doi:10.1177/1177391x0700100002 · Cited by 108
“(47) Moreover, it has been reported that S1P induces S1P1 internalization and recycling while FTY720-P induces S1P1 internalization and degradation.”
BackgroundEndothelial Functions of Sphingosine-1-phosphate
Lucke, S., & Levkau, B. (2010) · Cellular Physiology and Biochemistry · doi:10.1159/000315109 · Cited by 104
Xiong, Y., Piao, W., Brinkman, C. C., Li, L., Kulinski, J. M., Olivera, A., Cartier, A., Hla, T., Hippen, K. L., Blazar, B. R., et al. (2019) · Science Immunology · doi:10.1126/sciimmunol.aav1263 · Cited by 101
Sinha, R. K., Park, C., Hwang, I., Davis, M. D., & Kehrl, J. H. (2009) · Immunity · doi:10.1016/j.immuni.2008.12.018 · Cited by 103
“The other major model argues that S1PR1 on endothelial cells regulates lymphocyte egress ( Rosen et al., 2003 ).”
InfluentialHepatocyte Growth Factor Gene-Modified Mesenchymal Stem Cells Reduce Radiation-Induced Lung Injury
Wang, H., Yang, Y., Zhao, L., Xiao, F., Zhang, Q., Wen, M., Wu, C.-T., RuiYun, P. E. N. G., & Wang, L. (2013) · Human Gene Therapy · doi:10.1089/hum.2012.177 · Cited by 98
“It has been demonstrated that S1P1 plays a key role in angiogenesis and vascular maturation, as well as in the regulation of immune cell trafficking, endothelial barrier function, and vascular tone (Matloubian et al. , 2004; Sanna et al. , 2006).”
Xu, S., Liu, C., & Ji, H. (2019) · Stem Cells Translational Medicine · doi:10.1002/sctm.18-0038 · Cited by 98
Vascular permeability in the fibrotic lung
Probst, C. K., Montesi, S. B., Medoff, B. D., Shea, B. S., & Knipe, R. S. (2020) · European Respiratory Journal · doi:10.1183/13993003.00100-2019 · Cited by 98
Baumruker, T., Billich, A., & Brinkmann, V. (2007) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.16.3.283 · Cited by 94
“The requirement of S1P1 activation in this process was most convincingly demonstrated by using a S1P1 antagonist that blocks receptor activation by agonists and, as a consequence, produces a loss of capillary integrity and vascular leakage [30].”
BackgroundThe role of sphingolipids in respiratory disease
Yang, Y., & Uhlig, S. (2011) · Therapeutic Advances in Respiratory Disease · doi:10.1177/1753465811406772 · Cited by 93
“If these receptors are blocked in healthy animals, the consequence is pulmonary edema [Sanna et al. 2006].”
BackgroundShea, B. S., & Tager, A. M. (2012) · Proceedings of the American Thoracic Society · doi:10.1513/pats.201201-005aw · Cited by 91
“Interrupting S1P-S1P1 signaling with S1P1 receptor antagonists similarly increases vascular leak (101).”
BackgroundBurnier, L., & Mosnier, L. O. (2013) · Blood · doi:10.1182/blood-2013-03-488957 · Cited by 91
Sphingosine-1-phosphate in allergic responses, asthma and anaphylaxis
Oskeritzian, C. A., Milstien, S., & Spiegel, S. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.05.011 · Cited by 93
“Administration of selective S1P1 competitive antagonists to mice induces disruption of barrier integrity in pulmonary endothelium (Rosen et al., 2007; Sanna et al., 2006).”
BackgroundAlexander, S., Mathie, A. A., & Peters, J. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01649_3.x · Cited by 90
Sun, N., Shen, Y., Han, W., Shi, K., Wood, K., Fu, Y., Hao, J., Liu, Q., Sheth, K. N., Huang, D., et al. (2016) · Stroke · doi:10.1161/strokeaha.115.012236 · Cited by 88
Reines, I., Kietzmann, M., Mischke, R. H., Tschernig, T., Lüth, A., Kleuser, B., & Bäumer, W. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.454 · Cited by 89
“The concentration was selected, as both antagonists have Ki values in a low nanomolar range at the S1P1 (Davis et al., 2005, Sanna et al., 2006).”
Wang, Q., Alshaker, H. A., Böhler, T., Srivats, S., Chao, Y., Cooper, C., & Pchejetski, D. (2017) · Scientific Reports · doi:10.1038/s41598-017-06142-x · Cited by 90
Kihara, A., & Igarashi, Y. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2008.05.003 · Cited by 85
Gonzalez‐Cabrera, P. J., Hla, T., & Rosen, H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610581200 · Cited by 85
Self-citationSphingosine-1-phosphate: A Janus-faced mediator of fibrotic diseases
Schwalm, S. A., Pfeilschifter, J. M., & Huwiler, A. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2012.07.022 · Cited by 84
“this finding, it was demonstrated that the S1P1 antagonistW146 caused pulmonary edema, which further stresses the importance of S1P1 receptor activation as a protective mechanism in maintaining normal barrier function of the pulmonary endothelium [104,105].”
BackgroundActions of a picomolar short-acting S1P1 agonist in S1P1-eGFP knock-in mice
Cahalan, S. M., Gonzalez‐Cabrera, P. J., Sarkisyan, G., Nguyen, N., Schaeffer, M., Huang, L., Yeager, A. R., Clemons, B., Scott, F. L., & Rosen, H. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.547 · Cited by 83
Self-citationWacker, B. K., Perfater, J. L., & Gidday, J. M. (2012) · Journal of Neurochemistry · doi:10.1111/jnc.12047 · Cited by 83
Metadata
- Authors
- Sanna, M. G., Wang, S.-K., Gonzalez-Cabrera, P. J., Don, A., Marsolais, D., Matheu, M. P., Wei, S. H., Parker, I., Jo, E., Cheng, W.-C., Cahalan, M. D., Wong, C.-H., & Rosen, H.
- Affiliations
- Scripps Research Institute (US)
- University of California, Irvine (US)
- Corresponding author
- Wong, Chi-Huey
- Rosen, Hugh
- ORCID
- Venue
- Nature Chemical Biology
- Published
- 2006-07-09
- Volume
- 2
- Issue
- 8
- Pages
- 434-441
- ISSN
- 1552-4450 (ISSN-L)
- OpenAlex
- W2151535044
- Cited by
- 406
- References
- 39
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 11 · 2023: 10 · 2022: 8 · 2021: 7 · 2020: 18 · 2019: 22 · 2018: 6 · 2017: 20 · 2016: 21 · 2015: 22 · 2014: 21 · 2013: 44 · 2012: 35
- FWCI
- 12.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Kyorin Pharmaceutical
- National Institutes of Health
- U.S. Public Health Service (NIMH-074404)
- National Institute of Mental Health
- National Institute of General Medical Sciences (GM-48071, GM-41514, R01GM041514)
- National Institute of Allergy and Infectious Diseases (AI-055509, R01AI055509)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Keywords
- sphingosine-1-phosphate, S1P1 receptor, lymphocyte egress, lymphocyte migration, capillary leak syndrome, vascular barrier, lymphocyte sequestration, pulmonary edema, two-photon imaging
- MeSH terms
- Anilides, Animals, Capillary Permeability, Cells, Cultured, Disease Models, Animal, Evans Blue, Cricetinae, Humans, Lymph Nodes, Lymphocytes, Lysophospholipids, Mice, Inbred C57BL, Models, Biological, Phenotype, Pulmonary Edema, Sphingosine, Stereoisomerism, CHO Cells, Receptors, Lysosphingolipid, Mice, Organophosphonates
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