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Histamine modulates γδ‐T lymphocyte migration and cytotoxicity, via G i and G s protein‐coupled signalling pathways

2010; Wiley; Volume: 161; Issue: 6 Linguagem: Inglês

10.1111/j.1476-5381.2010.00639.x

1476-5381

Kristina Truta‐Feles, Mariana Lagadari, Katja Lehmann, Luciana Berod, Susana Cubillos, Susann Piehler, Yared Herouy, Dagmar Barz, Thomas Kamradt, Azzam A. Maghazachi, Johannes Norgauer,

Receptor Mechanisms and Signaling

Background and purpose: The biogenic amine, histamine plays a pathophysiological regulatory role in cellular processes of a variety of immune cells. This work analyses the actions of histamine on γδ‐T lymphocytes, isolated from human peripheral blood, which are critically involved in immunological surveillance of tumours. Experimental approach: We have analysed effects of histamine on the intracellular calcium, actin reorganization, migratory response and the interaction of human γδ T cells with tumour cells such as the A2058 human melanoma cell line, the human Burkitt's Non‐Hodgkin lymphoma cell line Raji, the T‐lymphoblastic lymphoma cell line Jurkat and the natural killer cell‐sensitive erythroleukaemia cell line, K562. Key results: γδ T lymphocytes express mRNA for different histamine receptor subtypes. In human peripheral blood γδ T cells, histamine stimulated Pertussis toxin‐sensitive intracellular calcium increase, actin polymerization and chemotaxis. However, histamine inhibited the spontaneous cytolytic activity of γδ T cells towards several tumour cell lines in a cholera toxin‐sensitive manner. A histamine H 4 receptor antagonist abolished the histamine induced γδ T cell migratory response. A histamine H 2 receptor agonist inhibited γδ T cell‐mediated cytotoxicity. Conclusions and implications: Histamine activated signalling pathways typical of chemotaxis (G i protein‐dependent actin reorganization, increase of intracellular calcium) and induced migratory responses in γδ T lymphocytes, via the H 4 receptor, whereas it down‐regulated γδ T cell mediated cytotoxicity through H 2 receptors and G s protein‐coupled signalling. Our data suggest that histamine activated γδ T cells could modulate immunological surveillance of tumour tissue.