Sphingosine 1-Phosphate, a Bioactive Sphingolipid Abundantly Stored in Platelets, Is a Normal Constituent of Human Plasma and Serum

1997 ◽  
Vol 121 (5) ◽  
pp. 969-973 ◽  
Author(s):  
Y. Yatomi ◽  
Y. Igarashi ◽  
L. Yang ◽  
N. Hisano ◽  
R. Qi ◽  
...  
1989 ◽  
Vol 119 (5) ◽  
pp. 713-721 ◽  
Author(s):  
Earl G. Burton ◽  
Grant L. Schoenhard ◽  
Julie A. Hill ◽  
R. Eric Schmidt ◽  
Jeremy D. Hribar ◽  
...  

2017 ◽  
Vol 18 (8) ◽  
pp. 1800 ◽  
Author(s):  
Emmanuel Egom ◽  
Ross Fitzgerald ◽  
Rebecca Canning ◽  
Rebabonye B. Pharithi ◽  
Colin Murphy ◽  
...  

2010 ◽  
Vol 299 (6) ◽  
pp. C1516-C1523 ◽  
Author(s):  
Robert Bucki ◽  
Alina Kułakowska ◽  
Fitzroy J. Byfield ◽  
Małgorzata Żendzian-Piotrowska ◽  
Marcin Baranowski ◽  
...  

Hypogelsolinemia is observed in patients with different states of acute or chronic inflammation such as sepsis, rheumatoid arthritis, and multiple sclerosis. In animal models of sepsis, repletion of plasma gelsolin reduces septic mortality. However, the functions of extracellular gelsolin and the mechanisms leading to its protective nature are poorly understood. Potential mechanisms involve gelsolin's extracellular actin scavenging function or its ability to bind bioactive lipids or proinflammatory mediators, which would limit inflammatory responses and prevent tissue damage. Here we report that human plasma gelsolin binds to sphingosine 1-phosphate (S1P), a pleiotropic cellular agonist involved in various immune responses, and to its synthetic structural analog FTY720P (Gilenya). The fluorescence intensity of a rhodamine B-labeled phosphatidylinositol 4,5-bisphosphate binding peptide derived from gelsolin and the optical density of recombinant human plasma gelsolin (rhpGSN) were found to decrease after the addition of S1P or FTY720P. Gelsolin's ability to depolymerize F-actin also decreased progressively with increasing addition of S1P. Transient increases in phosphorylation of extracellular signal-regulated kinase in bovine aortic endothelial cells (BAECs) after S1P treatment were inhibited by rhpGSN. The ability of S1P to increase F-actin content and the elastic modulus of primary astrocytes and BAECs was also prevented by rhpGSN. Evaluation of S1P and gelsolin levels in cerebrospinal fluid reveals a low concentration of gelsolin and a high concentration of S1P in samples obtained from patients suffering from lymphatic meningitis. These findings suggest that gelsolin-mediated regulation of S1P bioactivity may be important to maintain immunomodulatory balance at inflammatory sites.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Samar M. Hammad ◽  
Mohammed M. Al Gadban ◽  
Andrea J. Semler ◽  
Richard L. Klein

The physiological significance of sphingosine 1-phosphate (S1P) transport in blood has been debated. We have recently reported a comprehensive sphingolipid profile in human plasma and lipoprotein particles (VLDL, LDL, and HDL) using HPLC-MS/MS (Hammad et al., 2010). We now determined the relative concentrations of sphingolipids including S1P in the plasma subfraction containing lipoproteins compared to those in the remaining plasma proteins. Sphingomyelin and ceramide were predominantly recovered in the lipoprotein-containing fraction. Total plasma S1P concentration was positively correlated with S1P concentration in the protein-containing fraction, but not with S1P concentration in the lipoprotein-containing fraction. The percentage of S1P transported in plasma lipoproteins was positively correlated with HDL cholesterol (HDL-C) concentration; however, S1P transport in lipoproteins was not limited by the concentration of HDL-C in the individual subject. Thus, different plasma pools of S1P may have different contributions to S1P signaling in health and disease.


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