Apoptosis-inducing membrane vesicles. A novel agent with unique properties.
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.
Jodo
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Department of Medicine, the Arthritis Center, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
Xiao
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Hohlbaum
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Strehlow
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Marshak-Rothstein
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A
Ju
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D016475:3T3 Cells; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism*; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice
D000954:Antigens, Surface; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins