Heparan sulfate proteoglycans modulate monocyte migration across cerebral endothelium

Sarah Floris, Jacob van den Born, Susanne M A van der Pol, Christine D Dijkstra, Helga E De Vries

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Heparan sulfate proteoglycans (HSPGs) are known to participate in a wide range of biological events, including cellular trafficking. In this study we report that in situ cerebral blood vessels highly express HSPGs. Of the syndecan family, syndecan-2 is highly expressed on virtually all brain vessels and syndecan-1 and -3 are only present on larger blood vessels. These endothelial HSPGs have a functional role in monocyte diapedesis across brain endothelium, as assessed in our in vitro adhesion and migration assays. Our data indicate that heparin prevents monocyte adhesion to brain endothelium by interacting solely with the monocyte. Transendothelial migration of monocytes can be prevented by preincubation of brain endothelium with heparin by enzymatic removal of heparan sulphate side chains or by inhibition of cellular sulfation. Blocking of G-protein-dependent signaling in the monocytes prevented monocyte adhesion and migration to similar extent, suggesting that G-dependent signaling may be involved in HSPG-mediated monocyte adhesion and transendothelial migration. Our data demonstrate that brain endothelial HSPGs have a modulatory role in the transendothelial migration of monocytes in a direct and indirect fashion and may therefore contribute to the formation of neuroinflammatory lesions.

Original languageEnglish
Pages (from-to)780-90
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume62
Issue number7
Publication statusPublished - Jul 2003

Cite this

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title = "Heparan sulfate proteoglycans modulate monocyte migration across cerebral endothelium",
abstract = "Heparan sulfate proteoglycans (HSPGs) are known to participate in a wide range of biological events, including cellular trafficking. In this study we report that in situ cerebral blood vessels highly express HSPGs. Of the syndecan family, syndecan-2 is highly expressed on virtually all brain vessels and syndecan-1 and -3 are only present on larger blood vessels. These endothelial HSPGs have a functional role in monocyte diapedesis across brain endothelium, as assessed in our in vitro adhesion and migration assays. Our data indicate that heparin prevents monocyte adhesion to brain endothelium by interacting solely with the monocyte. Transendothelial migration of monocytes can be prevented by preincubation of brain endothelium with heparin by enzymatic removal of heparan sulphate side chains or by inhibition of cellular sulfation. Blocking of G-protein-dependent signaling in the monocytes prevented monocyte adhesion and migration to similar extent, suggesting that G-dependent signaling may be involved in HSPG-mediated monocyte adhesion and transendothelial migration. Our data demonstrate that brain endothelial HSPGs have a modulatory role in the transendothelial migration of monocytes in a direct and indirect fashion and may therefore contribute to the formation of neuroinflammatory lesions.",
keywords = "Animals, Cell Adhesion/drug effects, Cerebral Cortex/blood supply, Chemotaxis, Leukocyte/drug effects, Disease Models, Animal, Encephalitis/drug therapy, Encephalomyelitis, Autoimmune, Experimental, Endothelium, Vascular/drug effects, Extracellular Matrix/drug effects, GTP-Binding Proteins/antagonists & inhibitors, Heparan Sulfate Proteoglycans/metabolism, Heparin/pharmacology, Male, Membrane Glycoproteins/metabolism, Monocytes/drug effects, Protein Structure, Secondary/drug effects, Proteoglycans/metabolism, Rats, Rats, Inbred Lew, Rats, Wistar, Signal Transduction/drug effects, Sulfates/antagonists & inhibitors, Syndecan-2",
author = "Sarah Floris and {van den Born}, Jacob and {van der Pol}, {Susanne M A} and Dijkstra, {Christine D} and {De Vries}, {Helga E}",
year = "2003",
month = "7",
language = "English",
volume = "62",
pages = "780--90",
journal = "Journal of Neuropathology and Experimental Neurology",
issn = "0022-3069",
publisher = "Lippincott Williams and Wilkins",
number = "7",

}

Heparan sulfate proteoglycans modulate monocyte migration across cerebral endothelium. / Floris, Sarah; van den Born, Jacob; van der Pol, Susanne M A; Dijkstra, Christine D; De Vries, Helga E.

In: Journal of Neuropathology and Experimental Neurology, Vol. 62, No. 7, 07.2003, p. 780-90.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Heparan sulfate proteoglycans modulate monocyte migration across cerebral endothelium

AU - Floris, Sarah

AU - van den Born, Jacob

AU - van der Pol, Susanne M A

AU - Dijkstra, Christine D

AU - De Vries, Helga E

PY - 2003/7

Y1 - 2003/7

N2 - Heparan sulfate proteoglycans (HSPGs) are known to participate in a wide range of biological events, including cellular trafficking. In this study we report that in situ cerebral blood vessels highly express HSPGs. Of the syndecan family, syndecan-2 is highly expressed on virtually all brain vessels and syndecan-1 and -3 are only present on larger blood vessels. These endothelial HSPGs have a functional role in monocyte diapedesis across brain endothelium, as assessed in our in vitro adhesion and migration assays. Our data indicate that heparin prevents monocyte adhesion to brain endothelium by interacting solely with the monocyte. Transendothelial migration of monocytes can be prevented by preincubation of brain endothelium with heparin by enzymatic removal of heparan sulphate side chains or by inhibition of cellular sulfation. Blocking of G-protein-dependent signaling in the monocytes prevented monocyte adhesion and migration to similar extent, suggesting that G-dependent signaling may be involved in HSPG-mediated monocyte adhesion and transendothelial migration. Our data demonstrate that brain endothelial HSPGs have a modulatory role in the transendothelial migration of monocytes in a direct and indirect fashion and may therefore contribute to the formation of neuroinflammatory lesions.

AB - Heparan sulfate proteoglycans (HSPGs) are known to participate in a wide range of biological events, including cellular trafficking. In this study we report that in situ cerebral blood vessels highly express HSPGs. Of the syndecan family, syndecan-2 is highly expressed on virtually all brain vessels and syndecan-1 and -3 are only present on larger blood vessels. These endothelial HSPGs have a functional role in monocyte diapedesis across brain endothelium, as assessed in our in vitro adhesion and migration assays. Our data indicate that heparin prevents monocyte adhesion to brain endothelium by interacting solely with the monocyte. Transendothelial migration of monocytes can be prevented by preincubation of brain endothelium with heparin by enzymatic removal of heparan sulphate side chains or by inhibition of cellular sulfation. Blocking of G-protein-dependent signaling in the monocytes prevented monocyte adhesion and migration to similar extent, suggesting that G-dependent signaling may be involved in HSPG-mediated monocyte adhesion and transendothelial migration. Our data demonstrate that brain endothelial HSPGs have a modulatory role in the transendothelial migration of monocytes in a direct and indirect fashion and may therefore contribute to the formation of neuroinflammatory lesions.

KW - Animals

KW - Cell Adhesion/drug effects

KW - Cerebral Cortex/blood supply

KW - Chemotaxis, Leukocyte/drug effects

KW - Disease Models, Animal

KW - Encephalitis/drug therapy

KW - Encephalomyelitis, Autoimmune, Experimental

KW - Endothelium, Vascular/drug effects

KW - Extracellular Matrix/drug effects

KW - GTP-Binding Proteins/antagonists & inhibitors

KW - Heparan Sulfate Proteoglycans/metabolism

KW - Heparin/pharmacology

KW - Male

KW - Membrane Glycoproteins/metabolism

KW - Monocytes/drug effects

KW - Protein Structure, Secondary/drug effects

KW - Proteoglycans/metabolism

KW - Rats

KW - Rats, Inbred Lew

KW - Rats, Wistar

KW - Signal Transduction/drug effects

KW - Sulfates/antagonists & inhibitors

KW - Syndecan-2

M3 - Article

VL - 62

SP - 780

EP - 790

JO - Journal of Neuropathology and Experimental Neurology

JF - Journal of Neuropathology and Experimental Neurology

SN - 0022-3069

IS - 7

ER -