Scavenging roles of chemokine receptors: chemokine receptor deficiency is associated with increased levels of ligand in circulation and tissues

Title

Scavenging roles of chemokine receptors: chemokine receptor deficiency is associated with increased levels of ligand in circulation and tissues

Creator

Cardona A E; Sasse M E; Liu L P; Cardona S M; Mizutani M; Savarin C; Hu T; Ransohoff R M

Publisher

Blood

Date

2008
2008-07

Description

In vitro studies have implicated chemokine receptors in consumption and clearance of specific ligands. We studied the role that various signaling chemokine receptors play during ligand homeostasis in vivo. We examined the levels of ligands in serum and CNS tissue in mice lacking chemokine receptors. Compared with receptor-sufficient controls, Cx3cr1(-/-) mice exhibited augmented levels of CX3CL1 both in serum and brain, and circulating levels of CXCL1 and CXCL2 were increased in Cxcr2(-/-) mice. CCR2-deficient mice showed significantly increased amounts of circulating CCL2 compared with wild-type mice. Cxcr3(-/-) mice revealed increased levels of circulating and brain CXCL10 after experimental autoimmune encephalomyelitis (EAE) induction. CCR2-deficient peripheral blood and resident peritoneal cells exhibited reduced binding capacity and biologic responses to the CCR1 ligand CCL3, suggesting that elevated levels of CCR2 ligands had down-regulated CCR1. The results indicate that signaling chemokine receptors clear chemokines from circulation and tissues. These homeostatic functions of signaling chemokine receptors need to be integrated into safety and efficacy calculations when considering therapeutic receptor blockade.

Subject

in-vitro; central-nervous-system; Hematology; blood-brain-barrier; ccx-ckr; cutting edge; d6; dendritic cell; experimental autoimmune encephalomyelitis; immune-response; sjogrens-syndrome

Format

Journal Article or Conference Abstract Publication

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

256-263

Issue

2

Volume

112

Citation

Cardona A E; Sasse M E; Liu L P; Cardona S M; Mizutani M; Savarin C; Hu T; Ransohoff R M, “Scavenging roles of chemokine receptors: chemokine receptor deficiency is associated with increased levels of ligand in circulation and tissues,” NEOMED Bibliography Database, accessed May 9, 2021, https://neomed.omeka.net/items/show/8805.

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