Specialized roles of the chemokine receptors CCR1 and CCR5 in the recruitment of monocytes and T(H)1-like/CD45RO(+) T cells.
Chemokines and their receptors control the emigration of leukocytes during inflammation. The role of the RANTES (regulated on activation normal T-cell expressed and secreted) receptors CCR1 and CCR5 in the selective recruitment of monocytes, T(H)1-like T-cell clones, and peripheral T cells enriched for CD45RO(+) "memory" cells were tested in a system in which arrest under flow conditions is triggered by RANTES immobilized to activated endothelium. With the use of selective nonpeptide receptor antagonists or blocking antibodies, it was found that the RANTES-induced arrest of these cells was mediated predominantly by CCR1. In contrast, CCR5 mainly contributed to the spreading in shear flow, and both CCR1 and CCR5 supported transendothelial chemotaxis toward RANTES. The data in this study reveal specialized roles of apparently redundant receptors in distinct steps of leukocyte trafficking and suggest that not all receptors currently used to define mononuclear cell subsets are involved in their direct recruitment from the circulation.
Weber
C
C
Institut für Prophylaxe der Kreislaufkrankheiten, Medizinische Poliklinik, and Institut für Immunologie, Ludwig-Maximilians-Universität München, Munich, Germany. christian.weber@klp.med.uni-muenchen.de
Weber
K S
KS
Klier
C
C
Gu
S
S
Wank
R
R
Horuk
R
R
Nelson
P J
PJ
D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology; D005434:Flow Cytometry; D018056:Hemorheology; D006801:Humans; D007156:Immunologic Memory; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D054389:Receptors, CCR1; D019713:Receptors, CCR5 / Q000235:genetics / Q000502:physiology*; D019707:Receptors, Chemokine / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013379:Substrate Specificity; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects*; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects*
C515300:CCR1 protein, human; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D054389:Receptors, CCR1; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D018799:Intercellular Adhesion Molecule-1