1. Blockade of signaling via the very late antigen (VLA-4) and its counterligand vascular cell adhesion molecule-1 (VCAM-1) causes increased T cell apoptosis in experimental autoimmune neuritis
- Author
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Ralf Gold, Leussink Vi, Pepinsky Rb, K.V. Toyka, Guido Stoll, Uwe K. Zettl, Lobb Rr, and Sebastian Jander
- Subjects
Integrins ,medicine.medical_specialty ,Adoptive cell transfer ,Time Factors ,T-Lymphocytes ,Receptors, Lymphocyte Homing ,Vascular Cell Adhesion Molecule-1 ,Apoptosis ,Integrin alpha4beta1 ,Pathology and Forensic Medicine ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Antigen ,Internal medicine ,Anti-Allergic Agents ,medicine ,Animals ,VCAM-1 ,Cell adhesion ,biology ,Cell adhesion molecule ,T lymphocyte ,Neuritis, Autoimmune, Experimental ,Rats ,Nitric oxide synthase ,Disease Models, Animal ,Endocrinology ,chemistry ,Rats, Inbred Lew ,Disease Progression ,biology.protein ,Cancer research ,Female ,Neurology (clinical) ,Signal Transduction - Abstract
We characterized the early effects of anti-very late antigen (VLA-4) and its counterligand vascular cell adhesion molecule-1 (VCAM-1) antibody therapy on T cell infiltration and apoptosis in adoptive transfer experimental autoimmune neuritis of female Lewis rats. At the peak of disease, animals were treated with anti-VCAM-1 monoclonal antibody (mAb), anti-VLA-4 mAb, or the respective isotype mAb controls 18, 12, or 6 h before perfusion. Anti-VCAM-1 led to a rapid, significant increase of apoptotic T cells in the sciatic nerve with a maximum after 6 h, preceding the significant decrease of T cell infiltration seen after 18 h. This was accompanied by a significant reduction in mRNA levels for IFN-gamma and inducible nitric oxide synthase. The results for anti-VLA-4 treatment showed a similar trend. The early increase of T cell apoptosis following disruption of VLA-4/VCAM-1 interaction may reflect a novel signaling component of proapoptotic pathways.
- Published
- 2002