How Blood Cells Control Vessel Leakiness

Reserachers have discovered how sphingosine-1-phosphate, a compound that affects immune cell trafficking and blood vessel integrity, is transported into the bloodstream.

AsianScientist (Nov. 16, 2017) – In a study published in Nature, scientists in Singapore have discovered how a potent signaling factor produced by blood cells enters into the general circulation to affect the immune system and vascular functions.

Sphingosine-1-phosphate (S1P) is a signaling lipid secreted by red blood cells and platelets. It is required as an extracellular signal for the trafficking of immune cells such as T- and B-cells in the circulation. Earlier studies have also revealed that the lack of S1P signaling is harmful to blood vessels, often resulting in vascular complications such as cardiovascular diseases and stroke.

For a long time, researchers have suspected that hematopoietic cells are the major producers of S1P. However, the molecular transport machinery by which S1P is released into the bloodstream remained unknown.

In this study, a team of researchers led by Assistant Professor Long N. Nguyen observed that mice lacking the major facilitator superfamily transporter 2b (Mfsd2b) protein in their blood cells had low levels of S1P in the circulation. They reported that the Mfsd2b pathway contributes approximately half of the plasma S1P pool.

Additionally, the scientists found that red blood cell counts were significantly reduced in Mfsd2b knockout mice, and while blood vessel leakiness was unaffected, the knockout mice were particularly sensitive to anaphylactic shock. These results suggested that inflammatory and vascular diseases could be treated by manipulating the level of circulating S1P.

Surprisingly, the researchers also discovered that Mfsd2b knockout mice were sensitive to chemotherapy and radiotherapy. This implies that patients receiving chemotherapy and radiotherapy treatments could benefit from interventions that elevate plasma S1P levels.

“We identified a critical molecular target for S1P production,” explained Nguyen of the Yong Loo Lin School of Medicine. “This opens up new avenues of investigation aimed at regulating S1P signaling for the treatment of various diseases.”



The article can be found at: Vu et al. (2017) Mfsd2b is Essential for the Sphingosine-1-phosphate Export in Erythrocytes and Platelets.

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Source: National University of Singapore; Photo: Shutterstock.
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