title: Expression of CCR6 and CD83 by cytokine-activated human neutrophils.
abstract: Polymorphonuclear leukocytes (PMNLs) are thought to be terminally differentiated, short-lived, and unable to actively synthesize new proteins or to interact with T cells. In the current study, it was found that PMNLs incubated with supernatants of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PHA-sup) expressed high levels of CCR6 mRNA. Neutralization with IgG against several cytokines revealed that tumor necrosis factor (TNF)-alpha was largely responsible for the PHA-sup-induced CCR6 mRNA expression. Among recombinant cytokines, TNF-alpha induced high levels of CCR6 mRNA expression, whereas interferon (IFN)-gamma induced low levels. The 2 cytokines together exhibited a considerable synergy. Cytokine-activated PMNLs expressed functional CCR6, as detected by the binding of sodium iodide I 125-labeled liver and activation-regulated chemokine (LARC) and dose-dependent migration toward LARC. The induction of CCR6 suggested that these cytokine-activated PMNLs have more similarities with dendritic cells (DCs) that express CCR6 in an immature stage. In fact, the activation of PMNLs with TNF-alpha and IFN-gamma induced the expression of CD83, a dominant cell-surface marker of DCs. When PMNLs were activated with granulocyte macrophage-colony-stimulating factor, TNF-alpha, and IFN-gamma, these cells expressed CD40 and HLA-DR in addition to CD83. Taken together, PMNLs, under appropriate conditions, can undergo a differentiation process characterized by the acquisition of new phenotypes and functions, and such differentiated PMNLs may play more active roles in the adaptive immune response. (Blood. 2000;96:3958-3963)
authors.affiliation: Laboratory of Molecular Immunoregulation, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yamashiro
authors.forename: J M
authors.initials: JM
authors.lastname: Wang
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.forename: W H
authors.initials: WH
authors.lastname: Gong
authors.forename: H
authors.initials: H
authors.lastname: Kamohara
authors.forename: T
authors.initials: T
authors.lastname: Yoshimura
mesh_terms: D015703:Antigens, CD; D002454:Cell Differentiation / Q000187:drug effects; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics*; D018375:Neutrophil Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D054418:Chemokine CCL20; D019742:Chemokines, CC; D016207:Cytokines; D007136:Immunoglobulins; D007371:Interferon-gamma; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen; C108355:CCL20 protein, human; C106311:CCR6 protein, human; C515370:CCR7 protein, human