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Publication : Interaction between CX3CL1 and CX3CR1 regulates vasculitis induced by immune complex deposition.

First Author  Morimura S Year  2013
Journal  Am J Pathol Volume  182
Issue  5 Pages  1640-7
PubMed ID  23470165 Mgi Jnum  J:195540
Mgi Id  MGI:5484733 Doi  10.1016/j.ajpath.2013.01.023
Citation  Morimura S, et al. (2013) Interaction between CX3CL1 and CX3CR1 Regulates Vasculitis Induced by Immune Complex Deposition. Am J Pathol 182(5):1640-7
abstractText  A type III hypersensitivity reaction induced by an immune complex, such as leukocytoclastic vasculitis, is mediated by inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. CX3CL1, a ligand for CX3C chemokine receptor 1 (CX3CR1), has recently been identified as a key mediator of leukocyte adhesion that functions without the recruitment of integrins or selectin-mediated rolling. To elucidate the role of CX3CL1 and CX3CR1 in the development of leukocytoclastic vasculitis, the cutaneous and peritoneal reverse Arthus reactions, classic experimental models for immune complex-mediated tissue injury, were examined in mice lacking CX3CR1. CX3CL1 expression in sera and lesional skin of patients with polyarteritis nodosa (PN) and healthy controls was also examined. Edema and hemorrhage were significantly reduced in CX3CR1(-/-) mice compared with wild-type mice. Infiltration of neutrophils and mast cells and expression of IL-6 and tumor necrosis factor-alpha were also decreased in CX3CR1(-/-) mice. CX3CL1 was expressed in endothelial cells during the cutaneous reverse Arthus reactions. Furthermore, serum CX3CL1 levels were significantly higher in patients with PN than in healthy controls. Endothelial cells in lesional skin of patients with PN strongly expressed CX3CL1. These results suggest that interactions between CX3CL1 and CX3CR1 may contribute to the development of leukocytoclastic vasculitis by regulating neutrophil and mast cell recruitment and cytokine expression.
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