title: Characterization of conventional and atypical receptors for the chemokine CCL2 on mouse leukocytes.
abstract: Chemokine-directed leukocyte migration is crucial for effective immune and inflammatory responses. Conventional chemokine receptors (cCKRs) directly control cell movement; atypical chemokine receptors (ACKRs) regulate coexpressed cCKRs; and both cCKRs and ACKRs internalize chemokines to limit their abundance in vivo, a process referred to as scavenging. A leukocyte's migratory and chemokine-scavenging potential is determined by which cCKRs and ACKRs it expresses, and by the ligand specificity, signaling properties, and chemokine internalization capacity of these receptors. Most chemokines can bind at least one cCKR and one ACKR. CCL2 can bind to CCR2 (a cCKR) and two ACKRs (ACKR1 and ACKR2). In this study, by using fluorescent CCL2 uptake to label cells bearing functional CCL2 receptors, we have defined the expression profile, scavenging activity, and ligand specificity of CCL2 receptors on mouse leukocytes. We show that qualitative and quantitative differences in the expression of CCR2 and ACKR2 endow individual leukocyte subsets with distinctive CCL2 receptor profiles and CCL2-scavenging capacities. We reveal that some cells, including plasmacytoid dendritic cells, can express both CCR2 and ACKR2; that Ly6C(high) monocytes have particularly strong CCL2-scavenging potential in vitro and in vivo; and that CCR2 is a much more effective CCL2 scavenger than ACKR2. We confirm the unique, overlapping, ligand specificities of CCR2 and ACKR2 and, unexpectedly, find that cell context influences the interaction of CCL7 and CCL12 with CCR2. Fluorescent chemokine uptake assays were instrumental in providing these novel insights into CCL2 receptor biology, and the sensitivity, specificity, and versatility of these assays are discussed.
authors.affiliation: Centre for Immunobiology, Institute for Infection, Immunity, and Inflammation, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Ford
authors.affiliation: Centre for Immunobiology, Institute for Infection, Immunity, and Inflammation, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom.
authors.forename: Vuk
authors.initials: V
authors.lastname: Cerovic
authors.affiliation: Centre for Immunobiology, Institute for Infection, Immunity, and Inflammation, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom.
authors.forename: Simon W F
authors.initials: SW
authors.lastname: Milling
authors.affiliation: Centre for Immunobiology, Institute for Infection, Immunity, and Inflammation, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom.
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Graham
authors.affiliation: Centre for Immunobiology, Institute for Infection, Immunity, and Inflammation, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom Robert.Nibbs@glasgow.ac.uk Chris.Hansell@glasgow.ac.uk.
authors.forename: Chris A H
authors.initials: CA
authors.lastname: Hansell
authors.affiliation: Centre for Immunobiology, Institute for Infection, Immunity, and Inflammation, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom Robert.Nibbs@glasgow.ac.uk Chris.Hansell@glasgow.ac.uk.
authors.forename: Robert J B
authors.initials: RJ
authors.lastname: Nibbs
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology*; D054410:Chemokine CCL7 / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*
chemical_list: C491224:Ccl12 protein, mouse; C491768:Ccl2 protein, mouse; C515451:Ccl7 protein, mouse; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D018945:Monocyte Chemoattractant Proteins; D019707:Receptors, Chemokine