Syndecan-4 as antithrombin receptor of human neutrophils.
Antithrombin inhibits chemokine-induced migration of neutrophils by activating heparan sulfate proteoglycan-dependent signaling. Mechanisms of antithrombin's effects on neutrophils were, therefore, studied by testing function and expression of heparan sulfate proteoglycans in RT-PCR or flow cytometry and cell migration assays, respectively. In vitro effects of antithrombin on human neutrophil migration in modified Boyden chambers were abolished by pretreating cells with heparinase-1, chondroitinase, sodium chlorate, and anti-syndecan-4 antibodies. Expression of syndecan-4 mRNA and protein in neutrophils was demonstrated in RT-PCR and anti-syndecan-4 immunoreactivity assay, respectively. In the presence of pentasaccharide, antithrombin lost its activity on the cells. Data suggest that antithrombin regulates neutrophil migration via effects of its heparin-binding site on cell surface syndecan-4.
Kaneider
N C
NC
Division of General Internal Medicine, Department of Internal Medicine, University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
Egger
P
P
Dunzendorfer
S
S
Wiedermann
C J
CJ
D000906:Antibodies / Q000494:pharmacology; D000991:Antithrombins / Q000494:pharmacology*; D001665:Binding Sites; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects; D002810:Chondroitinases and Chondroitin Lyases / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D019763:Heparin Lyase / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D009844:Oligosaccharides / Q000494:pharmacology; D011509:Proteoglycans / Q000276:immunology / Q000378:metabolism*; D053671:Syndecan-4
D000906:Antibodies; D000991:Antithrombins; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D011509:Proteoglycans; C508304:SDC4 protein, human; C417062:SR 90107A-ORG 31540; D053671:Syndecan-4; D006493:Heparin; D002810:Chondroitinases and Chondroitin Lyases; D019763:Heparin Lyase