[Frontiers in Bioscience E1, 26-35, June 1, 2009]

Chemokines in vasculitis

Kevin Sean Eardley1, Stuart William Smith2,3, Paul Cockwell2,4

1Renal Unit, Royal Shrewsbury Hospital, Mytton Oak Hospital, Shrewsbury, Shropshire, United Kingdom, 2Department of Nephrology, University Hospital Birmingham NHS Trust, Birmingham, United Kingdom, 3Division of Immunity and Infection and 4Division of Medical Sciences, University of Birmingham, Birmingham, United Kingdom


1. Abstract
2. Classification of vasculitis
2.1. Anti-neutrophil cytoplasmic antibodies (ANCA)
3. The pathology of ANCA-associated glomerulonephritis
4. Neutrophil-directed CXC chemokines and their receptors
5. Mononuclear cells
5.1. Mononuclear-cell directed chemokines and their receptors
5.1.1. MCP-1/CCL2, CCR2 and CCR5
5.1.2. Fractalkine/CX3CL1 and CX3CR1
5.1.3. CXCR3 and ligands
5.1.4. Redundancy
6. Serum and urine chemokine levels
7. Lessons from Giant Cell Arteritis
8. Kawasaki disease, Henoch Schonlein purpura and chemokine receptor polymorphisms
9. Conclusion
10. Acknowledgements
11. References


The systemic vasculitides are a group of diseases where the primary pathological process is inflammatory injury to blood vessel walls. Their clinical manifestations are highly variable and range from organ specific disease to a systemic illness that can lead, if untreated, to multi-organ failure and death. The kidneys are often involved in systemic vasculitis, particularly in small vessel vasculitis, where the glomerular capillary bed is a target for injury. This leads to a vasculitic glomerulonephritis, with focal segmental inflammation and perivascular leukocyte accumulation evolving to extracapillary accumulation of mononuclear cells (including crescents). The kinetics of leukocyte infiltration and involvement in this setting are in part dependent on the combinatorial expression of chemokines and their receptors. We discuss the evidence base for the role of the chemokine network in the renal disease of small vessel vasculitis and extend this to non-renal aspects of small vessel vasculitis other systemic vasculitides.