Apolipoprotein M-bound sphingosine-1-phosphate regulates blood-brain barrier paracellular permeability and transcytosis

TY - JOUR

T1 - Apolipoprotein M-bound sphingosine-1-phosphate regulates blood-brain barrier paracellular permeability and transcytosis

AU - Mathiesen Janiurek, Mette

AU - Soylu-Kucharz, Rana

AU - Christoffersen, Christina

AU - Kucharz, Krzysztof

AU - Lauritzen, Martin

N1 - © 2019, Mathiesen Janiurek et al.

PY - 2019/11/25

Y1 - 2019/11/25

N2 - The blood-brain barrier (BBB) is formed by the endothelial cells lining cerebral microvessels, but how blood-borne signaling molecules influence permeability is incompletely understood. We here examined how the apolipoprotein M (apoM)-bound sphingosine 1-phosphate (S1P) signaling pathway affects the BBB in different categories of cerebral microvessels using ApoM deficient mice (Apom-/-). We used two-photon microscopy to monitor BBB permeability of sodium fluorescein (376 Da), Alexa Fluor (643 Da), and fluorescent albumin (45 kDA). We show that BBB permeability to small molecules increases in Apom-/- mice. Vesicle-mediated transfer of albumin in arterioles increased 3 to 10-fold in Apom-/- mice, whereas transcytosis in capillaries and venules remained unchanged. The S1P receptor 1 agonist SEW2871 rapidly normalized paracellular BBB permeability in Apom-/- mice, and inhibited transcytosis in penetrating arterioles, but not in pial arterioles. Thus, apoM-bound S1P maintains low paracellular BBB permeability in all cerebral microvessels and low levels of vesicle-mediated transport in penetrating arterioles.

AB - The blood-brain barrier (BBB) is formed by the endothelial cells lining cerebral microvessels, but how blood-borne signaling molecules influence permeability is incompletely understood. We here examined how the apolipoprotein M (apoM)-bound sphingosine 1-phosphate (S1P) signaling pathway affects the BBB in different categories of cerebral microvessels using ApoM deficient mice (Apom-/-). We used two-photon microscopy to monitor BBB permeability of sodium fluorescein (376 Da), Alexa Fluor (643 Da), and fluorescent albumin (45 kDA). We show that BBB permeability to small molecules increases in Apom-/- mice. Vesicle-mediated transfer of albumin in arterioles increased 3 to 10-fold in Apom-/- mice, whereas transcytosis in capillaries and venules remained unchanged. The S1P receptor 1 agonist SEW2871 rapidly normalized paracellular BBB permeability in Apom-/- mice, and inhibited transcytosis in penetrating arterioles, but not in pial arterioles. Thus, apoM-bound S1P maintains low paracellular BBB permeability in all cerebral microvessels and low levels of vesicle-mediated transport in penetrating arterioles.

U2 - 10.7554/eLife.49405

DO - 10.7554/eLife.49405

M3 - Journal article

C2 - 31763978

SN - 2050-084X

VL - 8

JO - eLife

JF - eLife

M1 - e49405

ER -