INVESTIGADORES
LAGADARI Mariana
artículos
Título:
Histamine modulates γδ-T lymphocyte migration and cytotoxicity, via Gi and Gs protein-coupled signalling pathways.
Autor/es:
TRUTA-FELES K; LAGADARI M; LEHMANN K; BEROD L; CUBILLOS S; PIEHLER S; HEROUY Y; BARZ D; KAMRADT T; MAGHAZACHI AA; NORGAUER J
Revista:
British Journal of Pharmacology
Editorial:
Wiley-Blackwell
Referencias:
Año: 2010 vol. 161 p. 1291 - 1300
ISSN:
1476-5381
Resumen:
Background and purpose: The biogenic amine, histamine plays a pathophysiological regulatory role in cellular processes ofa variety of immune cells. This work analyses the actions of histamine on gd-T lymphocytes, isolated from human peripheralblood, which are critically involved in immunological surveillance of tumours.Experimental approach: We have analysed effects of histamine on the intracellular calcium, actin reorganization, migratoryresponse and the interaction of human gd T cells with tumour cells such as the A2058 human melanoma cell line, the humanBurkitt?s Non-Hodgkin lymphoma cell line Raji, the T-lymphoblastic lymphoma cell line Jurkat and the natural killer cell-sensitiveerythroleukaemia cell line, K562.Key results: gd T lymphocytes express mRNA for different histamine receptor subtypes. In human peripheral blood gd T cells,histamine stimulated Pertussis toxin-sensitive intracellular calcium increase, actin polymerization and chemotaxis. However,histamine inhibited the spontaneous cytolytic activity of gd T cells towards several tumour cell lines in a cholera toxin-sensitivemanner. A histamine H4 receptor antagonist abolished the histamine induced gd T cell migratory response. A histamine H2receptor agonist inhibited gd T cell-mediated cytotoxicity.Conclusions and implications: Histamine activated signalling pathways typical of chemotaxis (Gi protein-dependent actinreorganization, increase of intracellular calcium) and induced migratory responses in gd T lymphocytes, via the H4 receptor,whereas it down-regulated gd T cell mediated cytotoxicity through H2 receptors and Gs protein-coupled signalling. Our datasuggest that histamine activated gd T cells could modulate immunological surveillance of tumour tissue.
