Role of the heparan sulfate proteoglycan syndecan-1 (CD138) in delayed-type hypersensitivity.

Masouleh BK, Ten Dam GB, Wild MK, Seelige R, van der Vlag J, Rops AL, Echtermeyer FG, Vestweber D, van Kuppevelt TH, Kiesel L, Götte M

Forschungsartikel (Zeitschrift)

Zusammenfassung

The cell surface heparan sulfate proteoglycan syndecan-1 (CD138) modulates the activity of chemokines, cytokines, integrins, and other adhesion molecules which play important roles in the regulation of inflammation. We have previously shown that syndecan-1-deficient murine leukocytes display increased interactions with endothelial cells and increased diapedesis in vivo and in vitro. In this study, we demonstrate that syndecan-1 has an important function as a negative modulator in the murine contact allergy model of oxazolone-mediated delayed-type hypersensitivity (DTH). Following elicitation of the DTH response, syndecan-1-deficient mice showed an increase in leukocyte recruitment, resulting in an increased and prolonged edema formation. Expression of the cytokines TNF-alpha and IL-6 of the chemokines CCL5/RANTES and CCL-3/MIP-1alpha and of the adhesion molecule ICAM-1 were significantly increased in syndecan-1-deficient compared with wild-type mice. In wild-type mice, syndecan-1 mRNA and protein expression was reduced during the DTH response. The differentially increased adhesion of syndecan-1-deficient leukocytes to ICAM-1 was efficiently inhibited in vitro by CD18-blocking Abs, which emerges as one mechanistic explanation for the anti-inflammatory effects of syndecan-1. Collectively, our results show an important role of syndecan-1 in the contact DTH reaction, identifying syndecan-1 as a novel target in anti-inflammatory therapy.

Details zur Publikation

FachzeitschriftThe Journal of Immunology (J Immunol)
Jahrgang / Bandnr. / Volume182
Ausgabe / Heftnr. / Issue8
Seitenbereich4985-4993
StatusVeröffentlicht
Veröffentlichungsjahr2009
Sprache, in der die Publikation verfasst istEnglisch
DOI10.4049/jimmunol.0800574

Autor*innen der Universität Münster

Götte, Martin
Klinik für Frauenheilkunde und Geburtshilfe
Kiesel, Ludwig
Klinik für Frauenheilkunde und Geburtshilfe
Vestweber, Dietmar
Max-Planck-Institut für Molekulare Biomedizin