Farkas, Stefan and Hornung, Matthias and Sattler, Christine and Anthuber, Matthias and Gunthert, U. and Herfarth, Hans and Schlitt, Hans Juergen and Geissler, Edward K. and Wittig, B. M. (2005) Short-term treatment with anti-CD44v7 antibody, but not CD44v4, restores the gut mucosa in established chronic dextran sulphate sodium (DSS)-induced colitis in mice. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 142 (2). pp. 260-267. ISSN 0009-9104,
Full text not available from this repository. (Request a copy)Abstract
Increased expression of CD44 variant isoforms have been shown on the inflammatory infiltrates in human and mouse colitis and blockade or deletion of CD44 isoforms inhibit experimental colitis. The objective of this study was to find out if short-term treatment of CD44 antibodies specific to CD44v7, but not to other variant isoforms, suppresses leucocyte-endothelial interaction in chronic dextran sodium sulphate (DSS)-induced colitis in mice. Chronic colitis was induced by oral administration of four cycles of 5% DSS in BALB/c mice. Expression of CD44 was investigated on isolated mononuclear cells of the gut immune system. In established colitis, mice were treated with antibodies against CD44v7 or CD44v4 three times in 7 days. Intravital microscopy was used to study leucocyte-endothelial interactions and leucocyte extravasation. As a marker of inflammatory infiltrates myeloperoxidase was quantified in gut tissue. CD44-induced apoptosis was determined by fluorescence staining of hypodiploidic cell nuclei. In chronic DSS-induced colitis both CD44 variant isoforms, v4 and v7 were significantly up-regulated on mononuclear cells. However, whereas anti-CD44v7 antibody treatment induced a marked restoration of the gut mucosa and significantly reduced endothelial sticking and extravasation of circulating leucocyte in vivo (P < 0.01), application of anti-CD44v4 or an isotype control antibody had no anti-inflammatory effect. A significant reduction of myeloperoxidase activity was detected after blockade of CD44v7, but not v4. Short-term treatment with anti-CD44v7 antibody blocks T cell extravasation and recruitment to the intestinal mucosa and cures established experimental colitis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | T-CELL EXTRAVASATION; VARIANT ISOFORMS; IMMUNODEFICIENT MICE; ADHESION MOLECULES; HYALURONAN-BINDING; IMMUNE-RESPONSES; MONOCYTE CD44; INFLAMMATION; APOPTOSIS; OLIGONUCLEOTIDES; CD44 variant isoforms; CD44 variant therapy; chronic inflammatory bowel disease |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Apr 2021 09:56 |
| Last Modified: | 23 Apr 2021 09:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35456 |
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