Divergent effects of human lymphokine derived oligopeptides on PMNLs function of young and aged healthy subjects |
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| Authors: | M Hauck T Ful?p G Fóris A Le?vey |
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| Affiliation: | 1. Centro Retrovirus, Dipartimento di Ricerca Traslazionale, University of Pisa, Italy;2. Dipartimento Biotecnologie Mediche, Università di Siena, Siena, Italy;3. UO Virologia, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy;4. Scuola Superiore Sant’Anna, P.zza Martiri Della Libertà 3, Pisa, Italy;1. Department of Applied Chemistry, Kookmin University, Seongbuk-gu, Seoul 02707, Republic of Korea;2. Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seongbuk-gu, Seoul 02841, Republic of Korea;3. SG Medical, 3-11, Ogeum-ro 13-gil, Songpa-gu, Seoul, 05548, Republic of Korea;4. New Drug Development Center, Osong Medical Innovation Foundation, 123, Cheongju, Chungcheongbuk-do 28160, Republic of Korea;1. Institute of Cancer Studies, University of Manchester, Manchester, UK;2. The Christie NHS Foundation Trust, Manchester, UK;3. Imperial College Healthcare NHS Trust, London, UK;4. Cancer Research UK and UCL Cancer Clinical Trials Centre, London, UK;5. University of Liverpool and Clatterbridge Cancer Centre, Liverpool, UK;6. The Royal Marsden NHS Foundation Trust, London, UK;7. St James University Hospital, The Leeds Teaching Hospital Trust, Beckett Street, Leeds, UK;8. Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK;9. Nottingham City Hospital, Nottingham University Hospitals NHS Trust, Nottingham, UK;10. Hull York Medical School, Castle Hill Hospital, Hull, UK;11. Guy''s Hospital, Guy''s and St Thomas'' NHS Foundation Trust, London, UK;12. Kent Oncology Centre, Maidstone Hospital, Kent, UK;13. Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK;14. Southampton University Hospitals NHS Foundation Trust, Southampton, UK;15. Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK;p. UCL Cancer Institute, London, UK |
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| Abstract: | The effects of low molecular weight lymphokine-derived oligopeptides (LK-OPs) on PMNLs effector functions and receptor mediated biochemical events were studied in the case of healthy young and aged subjects. In the case of young subjects the low mol. wt. LK-OPs stimulated the Fc gamma receptor-mediated effector functions of PMNLs, whereas an inhibition was observed in PMNLs of the elderly (extracellular cytotoxicity and intracellular killing). The underlying biochemical events, induced by low mol. wt. LK-OPs stimulation, were also investigated. In PMNLs of young subjects the oxidative metabolism was stimulated (enhanced O2 consumption, O2 and H2O2 production) by low mol. wt. LK-OPs, while in elderly subjects it was inhibited. The cyclic nucleotides regulating the Fc gamma receptor mediated effector functions and the oxygen radicals formation showed an altered dynamic response under low mol. wt. LK-OPs stimulation with aging i.e. the cGMP level could not be changed at all. Our results suggest that low mol. wt. LK-OPs induced inhibition of Fc gamma receptor mediated effector functions with aging could be partly explained by an altered post receptorial coupling switch and as a consequence the lymphokines could not play their role of immunomodulators further impairing the altered immune response with aging. |
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