title: Cytokine-mediated regulation of CXCR4 expression in human neutrophils.
abstract: 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.
authors.affiliation: Department of Respiratory Medicine, University of Tokyo Graduate School of Medicine, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nagase
authors.forename: Misato
authors.initials: M
authors.lastname: Miyamasu
authors.forename: Masao
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Masako
authors.initials: M
authors.lastname: Imanishi
authors.forename: Nelson H
authors.initials: NH
authors.lastname: Tsuno
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Morita
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirai
mesh_terms: 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
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor