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*
First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan; and
Department of Pathology, University of Birmingham, Birmingham, United Kingdom
CD44 is a ubiquitous molecule known as a hyaluronan receptor.
However, the relevance of CD44 to inflammatory processes, for example,
rheumatoid synovitis, remains unclear. In this study, we propose a
novel function for CD44 using synovial cells from rheumatoid arthritis
(RA) patients and demonstrated that CD44 cross-linking augmented Fas
expression and subsequent Fas-mediated apoptosis of the cells: 1)
cross-linking of CD44 on RA synovial cells markedly augmented Fas
expression and its mRNA transcription; 2) engagement of CD44
up-regulated Fas on the cells within 3 h, much more than IL-1
and TNF-
did; 3) the Fas-mediated early apoptotic change of the
cells was amplified by CD44 cross-linking; and 4) hyaluronan,
especially when fragmented, also augmented Fas-mediated early apoptosis
of the cells. Based on these findings, we postulate a new concept: that
interaction of CD44 on RA synovial cells with hyaluronan fragments
present in the surrounding extracellular matrix augments Fas expression
as well as Fas-mediated apoptosis of synovial cells. This may lead to
spontaneous growth arrest through Fas-Fas ligand pathway observed in
synovial cells of RA synovitis in vivo.
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