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5.0 - 11th April 1999


Effect of in vitro aging on the modulation of protein and fibronectin biosynthesis by the elastin-laminin receptor in human skin fibroblasts.

Fodil-Bourahla I, Drubaix I, Robert L, Labat-Robert J

Laboratoire d'Immunologie du Vieillissement, Equipe de Biochimie du Tissu Conjonctif, Service d'ophtalmologie Hotel-Dieu, Paris, France.

Gerontology 1999 Jan-Feb;45(1):23-30

The 67-kD elastin-laminin receptor (ELR) subunit which carries the recognition site for elastin peptides (EP) is a lectin. Its binding with galactosides can modulate the kinetics of its interaction with its ligand, EP. In this study the biosynthesis of proteins, collagen and fibronectin were evaluated in the presence of agonists and antagonists of the receptor on human skin fibroblasts. The biosynthesis of total proteins determined by 3H-proline incorporation and of fibronectin (by immunoprecipitation) were shown to increase with passage number. The presence of 1 microg/ml kappa-elastin (EP) in the culture medium increased both total proteins and fibronectin biosynthesis. Melibiose, an agonist of the receptor at 5 microg/ml (140 microM), decreased both proteins and fibronectin biosynthesis in the culture medium of human skin fibroblast at the 10th and 15th passage. These results show that the ELR can control the biosynthetic mechanisms of some of the macromolecular constituents of extracellular matrix such as fibronectin and moderate its age and passage-dependent upregulation.

Effect of in vitro aging on the biosynthesis of glycosaminoglycans by human skin fibroblasts. Modulation by the elastin-laminin receptor.

Fodil-Bourahla I, Drubaix I, Robert L

Laboratoire Universitaire de Recherche sur les Therapeutiques Substitutives en Ophtalmologie, Hotel-Dieu, Paris, France.

Mech Ageing Dev 1999 Jan 15;106(3):241-60

The incorporation of a radioactive precursor 3H-glucosamine in glycoconjugates, essentially glycosaminoglycans (GAG) was evaluated in the culture medium and cell fraction of human skin fibroblasts. Using increasing passage numbers, we could estimate the effect of in vitro aging on these biosynthetic activities. The incorporation in different free (hyaluronan) and protein bound (proteoglycans) GAGs was evaluated after specific enzymatic digestion. Most newly synthesized GAGs were excreted in the extracellular medium. Incorporation of the tracer in hyaluronan, the major biosynthetic product, increased with passage number but its titratable concentration decreased with in vitro aging, suggesting a rapid post-synthetic degradation. The proportion of chondroitin sulfates 4 (A) and 6 (C) and heparan sulfate decreased and that of dermatan sulfate increased with increasing passage number. We explored the modulation of these biosynthetic activities by the elastin laminin receptor. Using agonists (elastin peptides) and an antagonist (melibiose) of the receptor, their action on GAG biosynthesis was evaluated. Both elastin peptides and melibiose increased incorporation of the tracer in GAGs, but only melibiose inhibited post-synthetic degradation of hyaluronan, therefore increasing its concentration. The effect of passage number on the receptor mediated modulations was also investigated.

Cell death by overload of the elastin-laminin receptor on human activated lymphocytes: protection by lactose and melibiose.

Peterszegi G, Texier S, Robert L

Hopital Hotel Dieu, Paris, France.

Eur J Clin Invest 1999 Feb;29(2):166-72

BACKGROUND: Activated human lymphocytes were shown to express the elastin-laminin receptor in vitro and also in vivo in atherosclerotic plaques. In the presence of the agonist, elastin peptides, this receptor was shown to mediate an increased cell proliferation and an increased synthesis and excretion of an elastase-type serine endopeptidase. In this study, we investigated the variation of the above reaction as a function of agonist concentration. MATERIALS AND METHODS: Human lymphocytes were obtained by tonsillectomy and cultured in the presence of phytohaemagglutinin and elastin peptides. Cell viability was evaluated by vital dye exclusion. Elastase and cathepsin G activities were determined in culture supernates and cell lysates using synthetic substrates. Apoptotic cells were identified by the TUNEL method and by electron microscopy. RESULTS: At increasing concentrations of elastin peptides, a dose-dependent increase in cell death was observed. Up to 100 micrograms mL-1 elastin peptides and an increasing fraction of lymphocytes were found permeable to trypan blue, and a large proportion was in apoptosis. Elastin peptide-induced cell death was inhibited by 1 microgram mL-1 lactose and melibiose. CONCLUSION: We describe here cell death of human activated lymphocytes expressing the elastin-laminin receptor in the presence of increasing concentrations of elastin peptides, agonists of the receptor. The mechanism of cell death appears to be related to the triggering of the release of elastase and free radicals mediated by the elastin-laminin receptor. Antagonists of this receptor, lactose and melibiose, protected the lymphocytes from the receptor-mediated cell death.



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