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-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.


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.


CONCLUSIONS
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.
Péterszegi
G
G
Hopital Hôtel Dieu, Paris, France.
Texier
S
S
Robert
L
L
D017209:Apoptosis / Q000187:drug effects*; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects; D004549:Elastin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007785:Lactose / Q000494:pharmacology*; D019272:Leukocyte Elastase / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008553:Melibiose / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017474:Receptors, Laminin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012697:Serine Endopeptidases; D014343:Trypan Blue / Q000378:metabolism
D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D017474:Receptors, Laminin; C054901:elastin-binding proteins; D004549:Elastin; D008553:Melibiose; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D019272:Leukocyte Elastase; D014343:Trypan Blue; D007785:Lactose