Sphingosine-1-phosphate modulation of basal permeability and acute inflammatory responses in rat venular microvessels
| Autor: | Twanda L. Thirkill, Roger H. Adamson, A Altangerel, Joyce F. Clark, Fitz Roy E Curry, R K Sarai |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Endothelium Physiology Fluorescent Antibody Technique Bradykinin Vascular permeability Biology Occludin Capillary Permeability chemistry.chemical_compound Venules Antigens CD Sphingosine Physiology (medical) Internal medicine Cell Adhesion medicine Animals Humans Mesentery Platelet Activating Factor Cells Cultured Inflammation Microscopy Confocal Platelet-activating factor Endothelial Cells Membrane Proteins Original Articles Cadherins Rats rac GTP-Binding Proteins Rac GTP-Binding Proteins Endothelial stem cell medicine.anatomical_structure Endocrinology Biochemistry chemistry Acute Disease biology.protein lipids (amino acids peptides and proteins) Lysophospholipids Cardiology and Cardiovascular Medicine Cortactin |
| Zdroj: | Cardiovascular Research. 88:344-351 |
| ISSN: | 1755-3245 0008-6363 |
| DOI: | 10.1093/cvr/cvq184 |
| Popis: | Aims Although several cultured endothelial cell studies indicate that sphingosine-1-phosphate (S1P), via GTPase Rac1 activation, enhances endothelial barriers, very few in situ studies have been published. We aimed to further investigate the mechanisms whereby S1P modulates both baseline and increased permeability in intact microvessels. Methods and results We measured attenuation by S1P of platelet-activating factor (PAF)- or bradykinin (Bk)-induced hydraulic conductivity ( L p) increase in mesenteric microvessels of anaesthetized rats. S1P alone (1–5 µM) attenuated by 70% the acute L p increase due to PAF or Bk. Immunofluorescence methods in the same vessels under identical experimental conditions showed that Bk or PAF stimulated the loss of peripheral endothelial cortactin and rearrangement of VE-cadherin and occludin. Our results are the first to show in intact vessels that S1P pre-treatment inhibited rearrangement of VE-cadherin and occludin induced by PAF or Bk and preserved peripheral cortactin. S1P (1–5 µM, 30 min) did not increase baseline L p. However, 10 µM S1P (60 min) increased L p two-fold. Conclusion Our results conform to the hypothesis that S1P inhibits acute permeability increase in association with enhanced stabilization of peripheral endothelial adhesion proteins. These results support the idea that S1P can be useful to attenuate inflammation by enhancing endothelial adhesion through activation of Rac-dependent pathways. |
| Databáze: | OpenAIRE |
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