CCR7 ligands, SLC/6Ckine/Exodus2/TCA4 and CKbeta-11/MIP-3beta/ELC, are chemoattractants for CD56(+)CD16(-) NK cells and late stage lymphoid progenitors.
Two human CC chemokines, SLC/6Ckine/Exodus2/TCA4 and CKbeta-11/MIP-3beta/ELC, are previously reported as efficacious chemoattractants for T- and B-cells and dendritic cells. SLC and CKbeta-11 share only 32% amino acid identity, but are ligands for the same chemokine receptor, CCR7. In this study, we examined chemotactic activity of SLC and CKbeta-11 for NK cells and lymphoid progenitors in bone marrow and thymus. It was found that these two CCR7 ligands are chemoattractants for neonatal cord blood and adult peripheral blood NK cells and cell lines. SLC and CKbeta-11 preferentially attract the CD56(+)CD16(-) NK cell subset over CD56(+)CD16(+) NK cells. SLC and CKbeta-11 also demonstrate selective chemotactic activity on late stage CD34(-)CD19(+)IgM- B-cell progenitors and CD4(+) and CD8(+) single-positive thymocytes, but not early stage progenitors. It was noted that SLC is an efficient desensitizer of CKbeta-11-dependent NK cell chemotaxis, while CKbeta-11 is a weak desensitizer of SLC-dependent chemotaxis. Taken together, these results suggest that SLC and CKbeta-11 have the potential to control trafficking of NK cell subsets and late stage lymphoid progenitors in bone marrow and thymus.
Kim
C H
CH
Department of Microbiology/Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Pelus
L M
LM
Appelbaum
E
E
Johanson
K
K
Anzai
N
N
Broxmeyer
H E
HE
D019002:CD56 Antigen / Q000302:isolation & purification; D016764:Cell Polarity; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D003602:Cytotoxicity, Immunologic; D005089:Exocytosis; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology*; D008024:Ligands; D016131:Lymphocyte Subsets / Q000502:physiology; D011485:Protein Binding; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism*; D017452:Receptors, IgG / Q000302:isolation & purification; D013950:Thymus Gland / Q000166:cytology
C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; D019002:CD56 Antigen; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D008024:Ligands; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D017452:Receptors, IgG