PMID: 7540635Feb 1, 1995Paper

Treatment of immune cell-mediated liver damage by nonpeptidic mimetics of the extracellular matrix-associated Arg-Gly-Asp epitope

Journal of Hepatology
R HershkovizZ Halpern

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

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Citations

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)

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