Nature Immunology
2, 333 - 337 (2001)
doi:10.1038/86336
Extracellular matrix interacts with soluble CD95L: Retention and enhancement of cytotoxicityKazunori Aoki1, 3, Masayuki Kurooka1, Jian-Jun Chen1, Jerzy Petryniak1, Elizabeth G. Nabel2
& Gary J. Nabel11
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892-3005, USA. 2
National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. 3
Present address: National Cancer Center Research Institute, Section for Studies on Host-Immune Response, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
Correspondence should be addressed to Gary J. Nabel gnabel@nih.govFas 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.
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