Bruehl, Hilke and Cihak, Josef and Plachy, Jiri and Kunz-Schughart, Leoni and Niedermeier, Marianne and Denzel, Andrea and Gomez, Manuel Rodriguez and Talke, Yvonne and Luckow, Bruno and Stangassinger, Manfred and Mack, Matthias (2007) Targeting of Gr-l+,CCR2+ monocytes in collagen-induced arthritis. ARTHRITIS AND RHEUMATISM, 56 (9). pp. 2975-2985. ISSN 0004-3591,
Full text not available from this repository. (Request a copy)Abstract
Objective. The chemokine receptor CCR2 is highly expressed on monocytes and considered a promising target for treatment of rheumatoid arthritis. However, blockade of CCR2 with a monoclonal antibody (mAb) during progression of collagen -induced arthritis results in a massive aggravation of the disease. In this study we investigated why CCR2 antibodies have proin-flammatory effects, how these effects can be avoided, and whether CCR2+ monocytes are useful targets in the treatment of arthritis. Methods. Arthritis was induced in DBA/1 mice by immunization with type 11 collagen. Mice were treated with mAb against CCR2 (MC-21), IgE, or isotype control antibodies at various time points. Activation of basophils and depletion of monocyte subsets were determined by fluorescence- activated cell sorter analysis and enzyme-linked immunosorbent assay. Results. Crosslinkage of CCR2 activated basophils to release interieukin-6 (IL-6) and IL-4. In vivo, IL-6 release occurred only after exposure to high doses of MC-21, whereas application of low doses of the mAb circumvented the release of IL-6. Regardless of the dose level used, the antibody MC-21 efficiently depleted Gr-1 +,CCR2 + monocytes from the synovial tissue, peripheral blood, and spleen of DBA/1 mice. Activation of basophils with high doses of MC-21 or with antibodies against IgE resulted in a marked aggravation of collagen -induced arthritis and an increased release of IL-6. In contrast, low-dose treatment with MC-21 in this therapeutic setting had no effect on IL-6 and led to marked improvement of arthritis. Conclusion. These results show that depletion of CCR2+ monocytes may prove to be a therapeutic option in inflammatory arthritis, as long as the dose-dependent proinflammatory effects of CCR2 mAb are taken into account.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CHEMOKINE RECEPTOR CCR2; RHEUMATOID-ARTHRITIS; BLOOD MONOCYTES; BONE-MARROW; MAST-CELLS; CHEMOATTRACTANT PROTEIN-1; MONONUCLEAR-CELLS; MICE LACKING; T-CELLS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Dec 2020 08:36 |
| Last Modified: | 01 Dec 2020 08:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32229 |
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