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Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada
Activation of T cells by Ag or stimulation of monocytes with
inflammatory cytokines induces CD44 to bind to hyaluronan (HA), an
adhesion event implicated in leukocyte-leukocyte, leukocyte-endothelial
cell, and leukocyte-stromal cell interactions. We have previously shown
that TNF-
induces CD44 sulfation in a leukemic cell line, which
correlated with the induction of HA binding and CD44-mediated adhesion.
In this study, we establish that TNF-
and IFN-
induce HA binding
and the sulfation of CD44 in CD14+ PBMC, whereas no induced
HA binding or CD44 sulfation was observed in CD14- PBMC
stimulated with TNF-
. Treatment of cells with NaClO3, an
inhibitor of sulfation, prevented HA binding in a significant
percentage of CD14+ PBMC induced by TNF-
, LPS, IL-1
,
or IFN-
. Furthermore, stimulation with TNF-
or IFN-
in the
presence of NaClO3 reduced the ability of isolated CD44H to
bind HA, demonstrating a direct effect of CD44H sulfation on HA
binding. In contrast, the transient induction of HA binding in T cells
by PHA was not affected by NaClO3, suggesting that
activated T cells do not use sulfation as a mechanism to regulate HA
binding. Overall, these results demonstrate that inducible sulfation of
CD44H is one mechanism used by CD14+ peripheral blood
monocytes to induce HA binding in response to inflammatory agents such
as TNF-
and IFN-
.
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