Expression of a functional eotaxin (CC chemokine ligand 11) receptor CCR3 by human dendritic cells.
Critical to the function of Ag-presenting dendritic cells (DCs) is their capacity to migrate to lymphoid organs and to sites of inflammation. A final stage of development, termed maturation, yields DCs that are strong stimulators of T cell-mediated immunity and is associated with a remodeling of the cell surface that includes a change in the levels of expression of many molecules, including chemokine receptors. We show in this study that CCR3, a chemokine receptor initially discovered on eosinophils, is also expressed by human DCs that differentiate from blood monocytes, DCs that emigrate from skin (epidermal and dermal DCs), and DCs derived from CD34+ hemopoietic precursors in bone marrow, umbilical cord blood, and cytokine-elicited peripheral blood leukapheresis. Unlike other chemokine receptors, such as CCR5 and CCR7, the expression of CCR3 is not dependent on the state of maturation. All DC subsets contain a large intracellular pool of CCR3. The surface expression of CCR3 is not modulated following uptake of particulate substances such as zymosan or latex beads. CCR3 mediates in vitro chemotactic responses to the known ligands, eotaxin and eotaxin-2, because the DC response to these chemokines is inhibited by CCR3-specific mAbs. We postulate that expression of CCR3 may underlie situations where both DCs and eosinophils accumulate in vivo, such as the lesions of patients with Langerhans cell granulomatosis.
Beaulieu
Sylvie
S
Laboratory of Cellular Physiology and Immunology, The Rockefeller University and Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Medical College, Cornell University, New York, NY 10021, USA.
Robbiani
Davide F
DF
Du
Xixuan
X
Rodrigues
Elaine
E
Ignatius
Ralf
R
Wei
Yang
Y
Ponath
Paul
P
Young
James W
JW
Pope
Melissa
M
Steinman
Ralph M
RM
Mojsov
Svetlana
S
D018952:Antigens, CD34 / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D019742:Chemokines, CC / Q000378:metabolism* / Q000502:physiology; D002631:Chemotactic Factors, Eosinophil / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008863:Microspheres; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000502:physiology; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015054:Zymosan / Q000378:metabolism
D018952:Antigens, CD34; C515456:CCL11 protein, human; C515484:CCL24 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D015054:Zymosan