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Infection and Immunity, November 1999, p. 5573-5578, Vol. 67, No. 11
Department of Periodontology and
Endodontology, Okayama University Dental School, Okayama,
Japan1; Department of Periodontology and
Oral Biology, School of Dental Medicine, Boston University, Boston,
Massachusetts2; and Department of
Periodontology, The Hebrew University-Hadassah Faculty of Dental
Medicine, Jerusalem, Israel3
Received 5 May 1999/Returned for modification 1 July 1999/Accepted 30 July 1999
During infection, circulating blood monocytes migrate from the
vasculature to the extravascular compartments where they mature into
tissue macrophages. The maturation process prepares the cell to
actively participate in the inflammatory and the immune responses, and
many transcription factors have been found to be involved. Here we
report on a novel role for nuclear factor
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Differentiation of Monocytes to Macrophages Primes
Cells for Lipopolysaccharide Stimulation via Accumulation of
Cytoplasmic Nuclear Factor
B
B (NF-
B) in this
process. Its accumulation in the cytoplasm of differentiated macrophages is responsible for the enhanced ability of the cell to
respond to lipopolysaccharide (LPS) stimulation, as determined by tumor
necrosis factor alpha (TNF-
) secretion. Differentiation of the human
monocytic cell line THP-1 into macrophage-like cells was induced by
exposure of the cells to phorbol myristate acetate. DNA-bindable
NF-
B was not detected in the cytoplasm of undifferentiated THP-1
cells but accumulated in the cytoplasm of the cells following differentiation. No TNF-
was detected in the media of resting differentiated and nondifferentiated THP-1 cells. Stimulation with LPS
of differentiated cells induced the production of higher levels of
TNF-
than stimulation of nondifferentiated cells. This hyperresponsiveness to LPS was found in the mRNA and secreted TNF-
levels. Furthermore, stimulation with LPS induced the translocation of
NF-
B from the cytoplasm into the nucleus. This translocation process
was more rapid in the differentiated cells than in the nondifferentiated cells, and the resultant accumulated levels of
NF-
B in the nucleus were higher. The DNA-bindable NF-
B was identified as a heterodimer of p65 and p50. The results suggest that
NF-
B accumulation in the cytoplasm during maturation of monocytes to
macrophages primes the cells for enhanced responsiveness to LPS and
results in the rapid secretion of inflammatory mediators, such as
TNF-
, by mature macrophages following LPS challenge.
*
Corresponding author. Mailing address: Department of
Periodontology, The Hebrew University-Hadassah Faculty of Dental
Medicine, P.O. Box 12272, Jerusalem 91120, Israel. Phone: 972-2-6777826 or 972-2-6777827. Fax: 972-2-6438705. E-mail:
shapiral{at}cc.huji.ac.il.
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