Modulatory effects of octreotide on anti-CD3 and dexamethasone-induced apoptosis of murine thymocytes.
In an attempt to elucidate the effects of somatostatin on two crucial processes that regulated T-cell differentiation and selection in thymus in this study, we investigated in vivo and in vitro the effects of octreotide (SMS 201-995) on dynamics of apoptosis, induced by dexamethasone (DEX) or by anti-CD3 monoclonal antibodies (mAb). The data were estimated by analysis of absolute cellularity, DNA fragmentation and maturational stage of thymocytes, detecting the CD4 and/or CD8 and T cell receptor (TCR) expression on thymocytes. The results, obtained by estimation of subdiploid peak of DNA and ladder DNA formation, have shown that SMS given in vivo, may potentiate the early phase of DEX-induced nuclear fragmentation (at 24 h), accelerating simultaneously the elimination of thymic cells with double positive (DP) CD4high CD8high phenotype (expressed both as percentage and absolute number). On the contrary, SMS, given both in vivo and in vitro, down-regulated the late process (at 72 h) of nuclear fragmentation, induced by anti-CD3 mAb, minimizing simultaneously the elimination of DP cells (expressed both as percentage and absolute number). In anti-CD3-treated cultures of thymocytes, SMS retarded also the elimination of immature thymocytes, expressing the TRC alpha/betalow or intermediate phenotype. The data emphasize that octreotide might have important regulatory effect on processes of thymic differentiation and maturation, which are crucial for T cell selection, induction of tolerance and prevention of autoimmune diseases.
Trobonjaca
Z
Z
Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, Croatia.
Radosević-Stasić
B
B
Crncević
Z
Z
Rukavina
D
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D017252:CD3 Complex / Q000276:immunology*; D016516:CD4-CD8 Ratio; D053938:DNA Fragmentation; D003907:Dexamethasone / Q000494:pharmacology*; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D005938:Glucocorticoids / Q000494:pharmacology*; D006728:Hormones / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009707:Nucleosomes / Q000187:drug effects; D015282:Octreotide / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects*
D017252:CD3 Complex; D005456:Fluorescent Dyes; D005938:Glucocorticoids; D006728:Hormones; D009707:Nucleosomes; D003907:Dexamethasone; D015282:Octreotide