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Research Article Free access | 10.1172/JCI106598
Department of Medicine (Cell Biology and Genetics), New York University School of Medicine, New York 10016
Department of Environmental Medicine, New York University School of Medicine, New York 10016
Find articles by Hirschhorn, R. in: JCI | PubMed | Google Scholar
Department of Medicine (Cell Biology and Genetics), New York University School of Medicine, New York 10016
Department of Environmental Medicine, New York University School of Medicine, New York 10016
Find articles by Grossman, J. in: JCI | PubMed | Google Scholar
Department of Medicine (Cell Biology and Genetics), New York University School of Medicine, New York 10016
Department of Environmental Medicine, New York University School of Medicine, New York 10016
Find articles by Troll, W. in: JCI | PubMed | Google Scholar
Department of Medicine (Cell Biology and Genetics), New York University School of Medicine, New York 10016
Department of Environmental Medicine, New York University School of Medicine, New York 10016
Find articles by Weissmann, G. in: JCI | PubMed | Google Scholar
Published June 1, 1971 - More info
Previous work has suggested that intracellular proteolysis may play a role in lymphocyte stimulation. An inhibitor of proteolysis, epsilon amino caproic acid (EACA) was studied for its effect on the lymphocyte response to phytohemagglutinin (PHA). EACA was found to inhibit several parameters of lymphocyte stimulation (e.g. DNA, RNA, and protein synthesis as well as alterations in morphology) This inhibition was not due to diminished cellular viability and did not permanently impair the capacity of the lymphocyte to subsequently respond to PHA. Additionally, there was no evidence that this inhibition was due to other possible effects of EACA, such as alterations in Na+ — K+ transport, competitive amino acid deprivation or interference with PHA binding. Moreover, the inhibitors of proteolysis, tosyl arginine methyl ester (TAME), tosyl lysine chloromethyl ketone (TLCK), and tosyl phenyl-alanine chloromethyl ketone (TPCK), were also shown to inhibit lymphocyte stimulation.
EACA was most effective when added during the first 24 hr of stimulation. Therefore, these experiments support the hypothesis that proteolysis is an essential step in the early phase of lymphocyte activation.