Abstract
The etiology of T-cell-mediated liver injury involves the migration of immune cells, notably CD4+ T lymphocytes, into liver tissues. This process is mediated primarily by integrin-recognition of the sub-endothelium basement membranes and the extracellular matrix. The Arg-Gly-Asp-containing peptide, a major cell-adhesive ligand of extracellular matrix, is present in various plasma- and matrix-glycoproteins, such as fibronectin. Recently, we have described the design and usage of nonpeptide mimetics of Arg-Gly-Asp which bind specifically to integrins, and thereby, inhibit T cell immunity in vivo. We examined the efficacy of Arg-Gly-Asp-mimetics as potential therapeutic compounds for the treatment of experimental T-cell-mediated liver injury induced in mice by injection of Concanavalin-A. We now report that the Arg-Gly-Asp-mimetics specifically inhibited the binding of murine T cells to fibronectin, but did not affect the proliferative response of these cells in vitro. Intraperitoneal or oral administration of the Arg-Gly-Asp-mimetics but not the Arg-Gly-Asp-containing peptide, inhibited liver damage in mice if given before their inoculation with Con-A, as manifested by a lesser elevation in their serum levels of hepatic enzymes. ...Continue Reading
References
Jan 1, 1992·Digestion·T LaskusJ Cianciara
Apr 3, 1992·Cell·R O Hynes
Jul 1, 1992·The Journal of Clinical Investigation·G TiegsA Wendel
May 31, 1991·Biochemical and Biophysical Research Communications·H KumagaiM Ohba
Jan 1, 1992·Clinical & Experimental Metastasis·M S MurthyE F Scanlon
Jan 1, 1991·Journal of Gastroenterology and Hepatology·M Peters
Sep 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·T A FergusonT S Kupper
Aug 1, 1991·Seminars in Liver Disease·W C Maddrey, B Combes
Jul 1, 1991·Trends in Biochemical Sciences·S E D'SouzaE F Plow
Aug 2, 1990·Nature·T A Springer
Jan 1, 1991·The Journal of Clinical Investigation·E Ruoslahti
May 17, 1990·Nature·Y ShimizuS Shaw
Sep 1, 1989·The Journal of Cell Biology·C NathanS D Wright
Jan 1, 1988·Annual Review of Biochemistry·E Ruoslahti
Jan 1, 1987·Kardiologiia·Iu B BelousovE P Panchenko
Dec 2, 1993·International Journal of Cancer. Journal International Du Cancer·I HardanO Lider
Feb 2, 1993·Biochemistry·N GreenspoonO Lider
May 30, 2013·Carcinogenesis·Mei ChengJiachun Lu
Citations
Mar 1, 1997·Immunology Letters·K IkedaM Takeuchi
Jun 1, 1996·Journal of Hepatology·R BruckZ Halpern
Dec 2, 1998·Journal of Hepatology·H IwamotoH Nawata
Jan 18, 2005·Peptides·Bin ZhangZhigang Tian
Dec 5, 2012·Biochemical and Biophysical Research Communications·Fuyuki F InagakiAtsushi Miyajima
Apr 28, 2012·Immunopharmacology and Immunotoxicology·Chenghu LiuLining Zhang
Nov 23, 2013·JACC. Cardiovascular Interventions·Jolanta M Siller-MatulaUNKNOWN EPA (European Platelet Academy)