The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
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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Self-citationRetractedLymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1
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Sphingosine-1-phosphate: an enigmatic signalling lipid
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Alteration of Lymphocyte Trafficking by Sphingosine-1-Phosphate Receptor Agonists
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Self-citationCD69 acts downstream of interferon-α/β to inhibit S1P1 and lymphocyte egress from lymphoid organs
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Self-citationVascular reactions to histamine, histamine‐liberator and leukotaxine in the skin of guinea‐pigs
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Wymann, M. P., & Schneiter, R. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2335 · Cited by 1,314
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Promotion of Lymphocyte Egress into Blood and Lymph by Distinct Sources of Sphingosine-1-Phosphate
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Sphingosine-1-Phosphate and Lymphocyte Egress from Lymphoid Organs
Cyster, J. G., & Schwab, S. R. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075011 · Cited by 862
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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