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

Mathiesen Janiurek, Mette ; Soylu-Kucharz, Rana LU ; Christoffersen, Christina ; Kucharz, Krzysztof LU and Lauritzen, Martin (2019) In eLife 8.
Abstract

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... (More)

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.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ApoM-/-, C57B6/J, mouse, neuroscience
in
eLife
volume
8
publisher
eLife Sciences Publications
external identifiers
  • pmid:31763978
  • scopus:85075496191
ISSN
2050-084X
DOI
10.7554/eLife.49405
language
English
LU publication?
yes
id
e4792b33-44e9-4835-b59a-a34876e777ed
date added to LUP
2019-12-04 15:56:03
date last changed
2024-10-03 18:11:06
@article{e4792b33-44e9-4835-b59a-a34876e777ed,
  abstract     = {{<p>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.</p>}},
  author       = {{Mathiesen Janiurek, Mette and Soylu-Kucharz, Rana and Christoffersen, Christina and Kucharz, Krzysztof and Lauritzen, Martin}},
  issn         = {{2050-084X}},
  keywords     = {{ApoM-/-; C57B6/J; mouse; neuroscience}},
  language     = {{eng}},
  month        = {{11}},
  publisher    = {{eLife Sciences Publications}},
  series       = {{eLife}},
  title        = {{Apolipoprotein M-bound sphingosine-1-phosphate regulates blood-brain barrier paracellular permeability and transcytosis}},
  url          = {{http://dx.doi.org/10.7554/eLife.49405}},
  doi          = {{10.7554/eLife.49405}},
  volume       = {{8}},
  year         = {{2019}},
}