• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Extracellular matrix interacts with soluble CD95L: retention and enhancement of cytotoxicity.

Fas ligand (CD95L) is synthesized both on the cell surface membrane and in a soluble form. Although CD95L contributes to immune privilege in the cornea and testis, the functions of these alternatively processed proteins are not well understood. Some reports suggest that the cytotoxicity of soluble CD95L is insignificant, whereas others show potent responses in vivo, including hepatocyte apoptosis that causes liver failure. We show here that extracellular matrix proteins interact with soluble CD95L and potentiate its pro-apoptotic activity. The cytotoxicity of supernatants from CD95L-expressing cells was increased by incubation on tissue culture plates coated with these matrix proteins; this effect was mediated by trimeric soluble CD95L. With the use of immunoprecipitation, it was found that CD95L binds directly to fibronectin. In addition, immunohistochemical analysis of the cornea revealed that soluble CD95L binds primarily to extracellular matrix. The retention of soluble CD95L on extracellular matrices is likely to play an important role in the development of peripheral tolerance in immune-privileged sites.

Pubmed ID: 11276204

Authors

  • Aoki K
  • Kurooka M
  • Chen JJ
  • Petryniak J
  • Nabel EG
  • Nabel GJ

Journal

Nature immunology

Publication Data

April 29, 2001

Associated Grants

None

Mesh Terms

  • Animals
  • Apoptosis
  • Base Sequence
  • Cell Line
  • Cytotoxicity, Immunologic
  • DNA Primers
  • Extracellular Matrix
  • Eye
  • Fas Ligand Protein
  • Humans
  • Immune Tolerance
  • Ligands
  • Male
  • Membrane Glycoproteins
  • Mice
  • Mutagenesis, Site-Directed
  • Signal Transduction
  • Solubility
  • Testis