Cytokine-mediated regulation of CXCR4 expression in human neutrophils.
Several lines of evidence have suggested that a CXC chemokine receptor 4 (CXCR4)/stromal cell-derived factor-1 [SDF-1; CXC chemokine ligand 12 (CXCL12)] pair is involved in baseline trafficking of leukocytes into extravascular tissues and that modulation of surface CXCR4 expression may represent an alternative mechanism for control of cell-specific biological responses to SDF-1/CXCL12. We explored the regulation of CXCR4 expression by cytokines in polymorphonuclear neutrophils (PMNs). No significant surface expression of CXCR4 in freshly isolated PMNs was detected, but expression became apparent gradually during incubation. SDF-1alpha/CXCL12 initiated Ca2+ mobilization and migratory responses in 20 h cultured PMNs. The surface CXCR4 expression was suppressed most potently by interferon-gamma (IFN-gamma). IFN-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), and G-CSF also inhibited spontaneous CXCR4 expression. Real-time, quantitative PCR experiments revealed that a spontaneous increase and an IFN-gamma-mediated decrease in surface CXCR4 paralleled changes in the CXCR4 mRNA level. These results on PMNs support the argument that the SDF-1 (CXCL12)/CXCR4 system is regulated by cell type-specific mechanisms.
Nagase
Hiroyuki
H
Department of Respiratory Medicine, University of Tokyo Graduate School of Medicine, Japan.
Miyamasu
Misato
M
Yamaguchi
Masao
M
Imanishi
Masako
M
Tsuno
Nelson H
NH
Matsushima
Kouji
K
Yamamoto
Kazuhiko
K
Morita
Yutaka
Y
Hirai
Koichi
K
D016207:Cytokines / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics
D016207:Cytokines; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor