CX3CR1 reduces Ly6Chigh-monocyte motility within and release from the bone marrow after chemotherapy in mice.

Abstract

The chemokine receptor CCR2 controls the release of Ly6C(high) monocytes from the bone marrow and their recruitment to sites of inflammation. A second chemokine receptor, CX3CR1, is differentially expressed on monocyte subsets. We examined the role of CX3CR1 in monocyte trafficking during the recovery phase after cyclophosphamide (CP)-induced myeloablation and observed that, in the absence of CCR2, Ly6C(high) monocytes accumulated in the bone marrow and peripheral reconstitution was severely impaired compared with wild-type (WT) mice. In contrast, in the absence of CX3CR1, Ly6C(high) monocytes accumulated less rapidly in the marrow but recovered faster in the blood and were more recruited into the spleen, suggesting an opposite action between CCR2 and CX3CR1 in myelorestoration. During the recovery phase, marrow medullar monocytes displayed lower CX3CR1 expression and reduced their adherence to coated CX3CL1. Intravital imaging of the bone marrow showed that CP treatment impacts monocyte trafficking between the parenchyma and the vasculature. Medullar monocytes in CX3CR1(-/-) mice and mice treated with a specific antagonist of CX3CR1 displayed increased mean velocity and displacement and a reduced arrest coefficient compared with WT mice. This study indicates that CX3CR1 reduces the motility of Ly6C(high) monocytes in the bone marrow and thereby controls their release.

• Authors: Sébastien Jacquelin, Fabrice Licata, Karim Dorgham, Patricia Hermand, Lucie Poupel, Elodie Guyon, Philippe Deterre, David A Hume, Christophe Combadière, Alexandre Boissonnas
• Journal: Blood (Blood) Vol. 122 Issue 5 Pg. 674-83 (Aug 01 2013) ISSN: 1528-0020 [Electronic] United States
• PMID: 23775714 (Publication Type: Journal Article)

Chemical References

• Antigens, Ly
• Antineoplastic Agents
• CX3C Chemokine Receptor 1
• Cx3cr1 protein, mouse
• Ly-6C antigen, mouse
• Receptors, Chemokine

Topics

• Animals
• Antigens, Ly (metabolism)
• Antineoplastic Agents (pharmacology)
• Bone Marrow (drug effects, metabolism, physiology)
• Bone Marrow Cells (drug effects, metabolism, physiology)
• CX3C Chemokine Receptor 1
• Cell Adhesion (drug effects, genetics)
• Cell Movement (drug effects, genetics)
• Cells, Cultured
• Chemotaxis, Leukocyte (drug effects, genetics)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Monocytes (drug effects, metabolism, physiology)
• Receptors, Chemokine (genetics, metabolism, physiology)