---
_id: '2214'
abstract:
- lang: eng
  text: A hallmark of immune cell trafficking is directional guidance via gradients
    of soluble or surface bound chemokines. Vascular endothelial cells produce, transport
    and deposit either their own chemokines or chemokines produced by the underlying
    stroma. Endothelial heparan sulfate (HS) was suggested to be a critical scaffold
    for these chemokine pools, but it is unclear how steep chemokine gradients are
    sustained between the lumenal and ablumenal aspects of blood vessels. Addressing
    this question by semi-quantitative immunostaining of HS moieties around blood
    vessels with a pan anti-HS IgM mAb, we found a striking HS enrichment in the basal
    lamina of resting and inflamed post capillary skin venules, as well as in high
    endothelial venules (HEVs) of lymph nodes. Staining of skin vessels with a glycocalyx
    probe further suggested that their lumenal glycocalyx contains much lower HS density
    than their basolateral extracellular matrix (ECM). This polarized HS pattern was
    observed also in isolated resting and inflamed microvascular dermal cells. Notably,
    progressive skin inflammation resulted in massive ECM deposition and in further
    HS enrichment around skin post capillary venules and their associated pericytes.
    Inflammation-dependent HS enrichment was not compromised in mice deficient in
    the main HS degrading enzyme, heparanase. Our results suggest that the blood vasculature
    patterns steep gradients of HS scaffolds between their lumenal and basolateral
    endothelial aspects, and that inflammatory processes can further enrich the HS
    content nearby inflamed vessels. We propose that chemokine gradients between the
    lumenal and ablumenal sides of vessels could be favored by these sharp HS scaffold
    gradients.
acknowledgement: Michael Sixt's research is supported by the European Research Council
  (ERC Starting grant).
article_number: e85699
article_processing_charge: No
author:
- first_name: Liat
  full_name: Stoler Barak, Liat
  last_name: Stoler Barak
- first_name: Christine
  full_name: Moussion, Christine
  id: 3356F664-F248-11E8-B48F-1D18A9856A87
  last_name: Moussion
- first_name: Elias
  full_name: Shezen, Elias
  last_name: Shezen
- first_name: Miki
  full_name: Hatzav, Miki
  last_name: Hatzav
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
- first_name: Ronen
  full_name: Alon, Ronen
  last_name: Alon
citation:
  ama: Stoler Barak L, Moussion C, Shezen E, Hatzav M, Sixt MK, Alon R. Blood vessels
    pattern heparan sulfate gradients between their apical and basolateral aspects.
    <i>PLoS One</i>. 2014;9(1). doi:<a href="https://doi.org/10.1371/journal.pone.0085699">10.1371/journal.pone.0085699</a>
  apa: Stoler Barak, L., Moussion, C., Shezen, E., Hatzav, M., Sixt, M. K., &#38;
    Alon, R. (2014). Blood vessels pattern heparan sulfate gradients between their
    apical and basolateral aspects. <i>PLoS One</i>. Public Library of Science. <a
    href="https://doi.org/10.1371/journal.pone.0085699">https://doi.org/10.1371/journal.pone.0085699</a>
  chicago: Stoler Barak, Liat, Christine Moussion, Elias Shezen, Miki Hatzav, Michael
    K Sixt, and Ronen Alon. “Blood Vessels Pattern Heparan Sulfate Gradients between
    Their Apical and Basolateral Aspects.” <i>PLoS One</i>. Public Library of Science,
    2014. <a href="https://doi.org/10.1371/journal.pone.0085699">https://doi.org/10.1371/journal.pone.0085699</a>.
  ieee: L. Stoler Barak, C. Moussion, E. Shezen, M. Hatzav, M. K. Sixt, and R. Alon,
    “Blood vessels pattern heparan sulfate gradients between their apical and basolateral
    aspects,” <i>PLoS One</i>, vol. 9, no. 1. Public Library of Science, 2014.
  ista: Stoler Barak L, Moussion C, Shezen E, Hatzav M, Sixt MK, Alon R. 2014. Blood
    vessels pattern heparan sulfate gradients between their apical and basolateral
    aspects. PLoS One. 9(1), e85699.
  mla: Stoler Barak, Liat, et al. “Blood Vessels Pattern Heparan Sulfate Gradients
    between Their Apical and Basolateral Aspects.” <i>PLoS One</i>, vol. 9, no. 1,
    e85699, Public Library of Science, 2014, doi:<a href="https://doi.org/10.1371/journal.pone.0085699">10.1371/journal.pone.0085699</a>.
  short: L. Stoler Barak, C. Moussion, E. Shezen, M. Hatzav, M.K. Sixt, R. Alon, PLoS
    One 9 (2014).
date_created: 2018-12-11T11:56:22Z
date_published: 2014-01-22T00:00:00Z
date_updated: 2025-09-29T11:30:42Z
day: '22'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1371/journal.pone.0085699
ec_funded: 1
external_id:
  isi:
  - '000330283100061'
file:
- access_level: open_access
  checksum: 84a8033bda2e07e39405f5acc85f4eca
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  creator: system
  date_created: 2018-12-12T10:07:48Z
  date_updated: 2020-07-14T12:45:33Z
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  file_name: IST-2016-433-v1+1_journal.pone.0085699.pdf
  file_size: 12634775
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file_date_updated: 2020-07-14T12:45:33Z
has_accepted_license: '1'
intvolume: '         9'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
project:
- _id: 25A76F58-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '289720'
  name: Stromal Cell-immune Cell Interactions in Health and Disease
publication: PLoS One
publication_status: published
publisher: Public Library of Science
publist_id: '4756'
pubrep_id: '433'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Blood vessels pattern heparan sulfate gradients between their apical and basolateral
  aspects
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 9
year: '2014'
...