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J. Biol. Chem., Vol. 276, Issue 43, 39938-39944, October 26, 2001
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From the Departments of The CD95 ligand (FasL) transmembrane protein is
found on activated T cells and cells outside the immune system. A
well-known turnover process of membrane FasL is mediated by matrix
metalloproteinase, which generates soluble FasL (sFasL). Here, we
demonstrate that membrane FasL turnover occurs effectively through the
release of membrane vesicles. Quantitative analysis indicates
that this process is as effective as sFasL release for FasL-3T3 cells
but somewhat less effective for FasL-expressing T cells. The
apoptosis-inducing membrane vesicles display unique properties not
found in FasL-expressing cells and sFasL. Unlike sFasL,
vesicle-associated FasL remained bioactive, killing the same panel of
targets that are susceptible to FasL-expressing cells. In contrast to
FasL-expressing T cells, FasL-mediated killing by vesicles do not
involve LFA-1/ICAM interaction and do not depend on de novo
protein synthesis. These observations indicate that the release of
FasL-bearing vesicles contributes to the turnover of cell-associated
FasL, but the impact of the bioactive FasL-expressing vesicles on the
function of cell-associated FasL is different from that of
sFasL.
Apoptosis-inducing Membrane Vesicles
A NOVEL AGENT WITH UNIQUE PROPERTIES*
§,,,
Medicine and
¶ Microbiology, the Arthritis Center, School of Medicine, Boston
University School of Medicine, Boston, Massachusetts 02118
*
This work was supported in part by National Institute of
Health Grants AI36938 and ES10244 (to S. T. J.) and GM58724 and
CA90691 (to A. M. R.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: K508. Arthritis
Center, 715 Albany Street, Boston University Medical Campus, Boston, MA
02118. Tel.: 617-638-4303; Fax: 617-638-5226; E-mail: jushyrte@acs.bu.edu
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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