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*
First Department of Internal Medicine, and
Clinical Laboratory, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu, Japan; and
Department of Pathology, University of Birmingham, Birmingham, United Kingdom
CD44 is a ubiquitous molecule also known as hyaluronic acid or
homing receptor. However, the cellular functions and its role in
inflammation, for example, rheumatoid synovitis, are currently unknown.
In this study, we propose a novel function for CD44. Using synovial
cells from rheumatoid arthritis (RA) patients, we demonstrated that
CD44 cross-linking and binding to hyaluronan augmented VCAM-1
expression and subsequently VCAM-1-mediated cell adhesion. Briefly, we
found that 1) rheumatoid synovial cells highly expressed CD44; 2)
cross-linking of CD44 markedly but transiently augmented VCAM-1
expression and its mRNA transcription much more than did IL-1ß and
TNF-
; 3) hyaluronan, especially when fragmented, also up-regulated
VCAM-1; 4) CD44 activated the transcription factor AP-1; and 5) the
integrin-dependent adhesive function of RA synovial cells to T cells
was also amplified by CD44 cross-linking. These results indicate that
the adhesion of RA synovial cells to matrices such as hyaluronic acid
through CD44 could up-regulate VCAM-1 expression and VCAM-1-mediated
adhesion to T cells, which might in turn cause activation of T cells
and synovial cells in RA synovitis. We therefore propose that such
cross-talking among distinct adhesion molecules may be involved in the
pathogenesis of inflammation, including RA
synovitis.
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