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Blood, 1 December 2000, Vol. 96, No. 12, pp. 3958-3963
PHAGOCYTES
Expression of CCR6 and CD83 by cytokine-activated
human neutrophils
Shigeo Yamashiro,
Ji-Ming Wang,
De Yang,
Wang-Hua Gong,
Hidenobu Kamohara, and
Teizo Yoshimura
From the Laboratory of Molecular Immunoregulation,
National Cancer Institute-Frederick Cancer Research and Development
Center, Frederick, MD.
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)- was largely
responsible for the PHA-sup-induced CCR6 mRNA expression. Among
recombinant cytokines, TNF- induced high levels of CCR6 mRNA
expression, whereas interferon (IFN)- 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- and IFN- induced the
expression of CD83, a dominant cell-surface marker of DCs. When PMNLs
were activated with granulocyte macrophage-colony-stimulating factor,
TNF- , and IFN- , 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.

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