Abstract
BackgroundSphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid mediator that regulates many physiological and pathological processes. It has been suggested that S1P gradient with high concentrations in the blood and lymphatic fluid and low concentrations in the peripheral tissue plays important roles in immune cell trafficking and potentially cancer progression. However, only a few reports have assessed S1P levels in the lymphatic fluid due to lack of an established easy-to-use method. Here, we report a simple technique for collection of lymphatic fluid to determine S1P.Materials and methodsLymphatic fluid was collected directly with a catheter needle (classical method) or was absorbed onto filter paper after incision of cisterna chyli (new method) in murine models. Blood, lymphatic fluid and mesenteric lymph nodes were corrected from wild type and sphingosine kinase 2 (SphK2) knockout mice to determine S1P levels by mass spectrometry.ResultsThe volume of lymphatic fluid collected by the new method was at least three times greater than those collected by the classical method. S1P concentrations in lymphatic fluid are lower than in blood and higher than in lymph nodes. Interestingly, S1P levels in lymphatic fluid from SphK2 knockout mice were significantly higher than those in wild type, suggesting an important role of SphK2 and/or SphK1 to regulate S1P levels in lymphatic fluid.ConclusionsIn agreement with the previous theory, our results confirm “S1P gradient” among blood, lymphatic fluid and peripheral lymphatic tissues. Convenient methods for collection and measurement of sphingolipids in lymphatic fluid are expected to provide new insights on functions of sphingolipids.
Highlights
Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid mediator that regulates many physiological and pathological processes including immune cell trafficking, inflammation, angio-/lymphangiogenesis, and cancer progression [1, 2, 3, 4, 5, 6]
These many pathological processes are regulated by S1P that is secreted from cells to the extracellular spaces and exerts its functions by binding to five specific G protein–coupled receptors (S1PR1-5) in autocrine and paracrine manners, a process known as “inside-out” signaling [1, 14, 15]
S1P is generated by two sphingosine kinases (SphK1 and sphingosine kinase 2 (SphK2)) inside cells, and secreted out of the cell to the extracellular spaces, such as interstitial fluid (IF) and lymphatic fluid [16]
Summary
Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid mediator that regulates many physiological and pathological processes including immune cell trafficking, inflammation, angio-/lymphangiogenesis, and cancer progression [1, 2, 3, 4, 5, 6]. Previous evidence suggested that the S1P gradient of high S1P concentrations in the circulation (blood and lymphatic fluid) plays an important role in immune cell trafficking [7, 17, 18, 19, 20] and potentially cancer progression. It has been suggested that S1P gradient with high concentrations in the blood and lymphatic fluid and low concentrations in the peripheral tissue plays important roles in immune cell trafficking and potentially cancer progression.
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