title: Angiogenin is upregulated during the alloreactive immune response and has no effect on the T-cell expansion phase, whereas it affects the contraction phase by inhibiting CD4+T-cell apoptosis.
abstract: Under growth conditions, angiogenin is translocated into the nucleus, where it enhances ribosomal RNA transcription, facilitating increased protein synthesis and cellular proliferation. During stress conditions, angiogenin is sequestered in the cytoplasm, where it cleaves transfer RNA (tRNA) to produce tRNA-derived, stress-induced small RNAs (tiRNAs) that inhibit global protein synthesis, but increase the translation of anti-apoptotic factors. In the present study, the role of angiogenin in the human alloreactive immune response was evaluated using mixed lymphocyte reactions (MLRs) and neamine, an inhibitor of angiogenin nuclear translocation. In MLRs, angiogenin production was significantly (P<0.001) increased compared with resting peripheral blood mononuclear cells. The addition of neamine had no effect on cell proliferation, but did significantly (P<0.001) increase expression of Bcl-2-associated X protein and protein levels of activated caspase-3 in CD4+T-cells isolated from the MLRs, indicating that angiogenin reduces apoptosis. In conclusion, angiogenin is upregulated during the alloreactive immune response, in which it does not affect the T-cell expansion phase, but inhibits the T-cell contraction phase by protecting against CD4+T-cell apoptosis.
authors.affiliation: Department of Nephrology, University of Thessaly Medical School, 41110 Larissa, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Eleftheriadis
authors.affiliation: Department of Nephrology, University of Thessaly Medical School, 41110 Larissa, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Pissas
authors.affiliation: Department of Nephrology, University of Thessaly Medical School, 41110 Larissa, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Sounidaki
authors.affiliation: Organ Transplant Unit, Hippokration General Hospital, Aristotle University of Thessaloniki Medical School, 54642 Thessaloniki, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Antoniadis
authors.affiliation: Department of Nephrology, University of Thessaly Medical School, 41110 Larissa, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Antoniadi
authors.affiliation: Department of Nephrology, University of Thessaly Medical School, 41110 Larissa, Greece.
authors.forename: Vassilios
authors.initials: V
authors.lastname: Liakopoulos
authors.affiliation: Department of Nephrology, University of Thessaly Medical School, 41110 Larissa, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Stefanidis
keywords: angiogenin; apoptosis; cluster of differentiation 4 positive T-cells; proliferation