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

Background Activated human lymphocytes were shown to express the elastin;la minin receptor in vitro and also in vivo in atherosclerotic plaques. In the presence of the agonist, elastin peptides, this receptor was shown to medi ate an increased cell proliferation and an increased synthesis and excretio n 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 ac tivities were determined in culture supernates and cell lysates using synth etic 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 mu g mL(-1) elastin peptides and an increasing fraction of lymphocytes were found permeable to trypan b lue, and a large proportion was in apoptosis. Elastin peptide-induced cell death was inhibited by 1 mu g mL(-1) lactose and melibiose. Conclusion We describe here cell death of human activated lymphocytes expre ssing the elastin-laminin receptor in the presence of increasing concentrat ions of elastin peptides, agonists of the receptor. The mechanism of cell d eath appears to be related to the triggering of the release of elastase and free radicals mediated by the elastin-laminin receptor. Antagonists of thi s receptor, lactose and melibiose, protected the lymphocytes from the recep tor-mediated cell death.