Expression of CCR6 and CD83 by cytokine-activated human neutrophils.

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)