Heparan sulfate proteoglycans modulate monocyte migration across cerebral endothelium.
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.
Floris
Sarah
S
Department of Molecular Cell Biology , Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
van den Born
Jacob
J
van der Pol
Susanne M A
SM
Dijkstra
Christine D
CD
De Vries
Helga E
HE
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D004681:Encephalomyelitis, Autoimmune, Experimental; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D017433:Protein Structure, Secondary / Q000187:drug effects / Q000502:physiology; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013431:Sulfates / Q000037:antagonists & inhibitors; D053669:Syndecan-2
D019812:Heparan Sulfate Proteoglycans; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508247:Sdc2 protein, rat; D013431:Sulfates; D053669:Syndecan-2; D006493:Heparin; D019204:GTP-Binding Proteins