Targeted deletion of CX3CR1 reveals a role for fractalkine in cardiac allograft rejection
| Autor: | Wayne W. Hancock, Israel F. Charo, Kerrie L. Faia, Christopher A. Haskell, David J. Salant, Vilmos Csizmadia, Wei Gao, Omar Fituri, James B. Rottman, Wendy Peters |
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| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Graft Rejection
Male Chemokine Encephalomyelitis Autoimmune Experimental CX3C Chemokine Receptor 1 Article Mice Glomerulonephritis Receptors HIV Cyclosporin a CX3CR1 MHC class I medicine Cell Adhesion Leukocytes Animals Receptors Cytokine Receptor Cells Cultured Mice Knockout Mice Inbred BALB C biology Chemokine CX3CL1 Experimental autoimmune encephalomyelitis Graft Survival Membrane Proteins General Medicine medicine.disease Oligodendrocyte Chemokines CX3C Transplantation Mice Inbred C57BL medicine.anatomical_structure Immunology Gene Targeting biology.protein Cyclosporine Cytokines Heart Transplantation Female Immunosuppressive Agents |
| Popis: | Fractalkine (Fk) is a structurally unusual member of the chemokine family. To determine its role in vivo, we generated mice with a targeted disruption of CX(3)CR1, the receptor for Fk. CX(3)CR1(-/-) mice were phenotypically indistinguishable from wild-type mice in a pathogen-free environment. In response to antibody-induced glomerulonephritis, CX(3)CR1(-/-) and CX(3)CR1(+/+) mice had similar levels of proteinuria and injury. CX(3)CR1(-/-) and CX(3)CR1(+/+) mice also developed similar levels of disease in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. We performed heterotopic MHC class I/II cardiac transplants from BALB/c mice into C57BL/6 mice. In the absence of cyclosporin A (CsA), there was no difference in graft survival time between CX(3)CR1(-/-) and CX(3)CR1(+/+) recipient mice. However, in the presence of subtherapeutic levels of CsA, graft survival time was significantly increased in the CX(3)CR1(-/-) mice. Characterization of cells infiltrating the grafts revealed a selective reduction in natural killer cells in the CX(3)CR1(-/-) recipients in the absence of CsA and a reduction in macrophages, natural killer cells, and other leukocytes in the presence of CsA. We conclude that Fk plays an important role in graft rejection. The development of CX(3)CR1 antagonists may allow reductions in the doses of immunosuppressive drugs used in transplantation. |
| Databáze: | OpenAIRE |
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