PMID- 11927659 OWN - NLM STAT- MEDLINE DCOM- 20020502 LR - 20081121 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 71 IP - 4 DP - 2002 Apr TI - Cytokine-mediated regulation of CXCR4 expression in human neutrophils. PG - 711-7 AB - 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. FAU - Nagase, Hiroyuki AU - Nagase H AD - Department of Respiratory Medicine, University of Tokyo Graduate School of Medicine, Japan. FAU - Miyamasu, Misato AU - Miyamasu M FAU - Yamaguchi, Masao AU - Yamaguchi M FAU - Imanishi, Masako AU - Imanishi M FAU - Tsuno, Nelson H AU - Tsuno NH FAU - Matsushima, Kouji AU - Matsushima K FAU - Yamamoto, Kazuhiko AU - Yamamoto K FAU - Morita, Yutaka AU - Morita Y FAU - Hirai, Koichi AU - Hirai K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Cytokines) RN - 0 (RNA, Messenger) RN - 0 (Receptors, CXCR4) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - 82115-62-6 (Interferon-gamma) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Cytokines/*pharmacology MH - Granulocyte Colony-Stimulating Factor/pharmacology MH - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology MH - Humans MH - Interferon-gamma/pharmacology MH - Neutrophils/*metabolism MH - RNA, Messenger/analysis MH - Receptors, CXCR4/*biosynthesis/genetics EDAT- 2002/04/03 10:00 MHDA- 2002/05/03 10:01 CRDT- 2002/04/03 10:00 PHST- 2002/04/03 10:00 [pubmed] PHST- 2002/05/03 10:01 [medline] PHST- 2002/04/03 10:00 [entrez] PST - ppublish SO - J Leukoc Biol. 2002 Apr;71(4):711-7.