Expression of CCR6 and CD83 by cytokine-activated human neutrophils

Polymorphonuclear leukocytes (PMNLs) are thought to be terminally different iated, short-lived, and unable to actively synthesize new proteins or to in teract with T cells, In the current study, it was found that PMNLs incubate d with supernatants of phytohemagglutinin (PHA)stimulated peripheral blood mononuclear cells (PHA-sup) expressed high levels of CCR6 mRNA, Neutralizat ion with IgG against several cytokines revealed that tumor necrosis factor (TNF)-alpha was largely responsible for the PHA-sup-induced CCR6 mRNA expre ssion. Among recombinant cytokines, TNF-alpha induced high levels of CCR6 m RNA expression, whereas interferon (IFN)-gamma induced low levels. The 2 cy tokines together exhibited a considerable synergy. Cytokine-activated PMNLs expressed functional CCR6, as detected by the binding of sodium iodide I 1 25-labeled liver and activation-regulated chemokine (LARC) and dose-depende nt migration toward LARC, The induction of CCR6 suggested that these cytoki ne-activated PMNLs have more similarities with dendritic cells (DCs) that e xpress 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-surfac e marker of DCs, When PMNLs were activated with granulocyte macrophage-colo ny-stimulating factor, TNF-alpha, and IFN-gamma, these cells expressed CD40 and HLA-DR in addition to CD83. Taken together, PMNLs, under appropriate c onditions, can undergo a differentiation process characterized by the acqui sition of new phenotypes and functions, and such differentiated PMNLs may p lay more active roles in the adaptive immune response. (C) 2000 by The Amer ican Society of Hematology.