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CCR2 and CXCR4 regulate peripheral blood monocyte pharmacodynamics and link to efficacy in experimental autoimmune encephalomyelitis by Yuanfan Wang; Long Cui; Waldemar Gonsiorek; Soo-Hong Min; Gopinadhan Anilkumar; Stuart Rosenblum; Joseph Kozlowski; Daniel Lundell; Jay S Fine; Ethan P Grant is a Medicine article available to read on EtoBox.
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## Abstract ## Background CCR2 plays a key role in regulating monocyte trafficking to sites of inflammation and therefore has been the focus of much interest as a target for inflammatory disease. ## Methods Here we examined the effects of CCR2 blockade with a potent small molecule antagonist to determine the pharmacodynamic consequences on the peripheral blood monocyte compartment in the context of acute and chronic inflammatory processes. ## Results We demonstrate that CCR2 antagonism __in vivo__ led to a rapid decrease in the number of circulating Ly6C^hi^ monocytes and that this decrease was largely due to the CXCR4-dependent sequestration of these cells in the bone marrow, providing pharmacological evidence for a mechanism by which monocyte dynamics are regulated __in vivo__. CCR2 antagonism led to an accumulation of circulating CCL2 and CCL7 levels in the blood, indicating a role for CCR2 in regulating the levels of its ligands under homeostatic conditions. Finally, we show that the pharmacodynamic changes due to CCR2 antagonism were apparent after chronic dosing in mouse experimental autoimmune encephalomyelitis, a model in which CCR2 blockade demonstrated a dramatic reductio
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- Author
- Yuanfan Wang; Long Cui; Waldemar Gonsiorek; Soo-Hong Min; Gopinadhan Anilkumar; Stuart Rosenblum; Joseph Kozlowski; Daniel Lundell; Jay S Fine; Ethan P Grant
- Publisher
- BioMed Central; Springer (Biomed Central Ltd.); [London]: BioMed Central, 2004-; Springer Science and Business Media LLC (ISSN 1476-9255)
- Published
- 2009
- Language
- EN
- Field
- Medicine (Life Sciences)