Alpha 7 nicotinic acetylcholine receptor modulates lymphocyte activation

DE ROSA, MARIA JOSE*; DIONISIO, LEONARDO*; AGRIELLO, EVANGELINA; BOUZAT, CECILIA; ESANDI, MARIA DEL CARMEN (*ESTOS AUTORES CONTRIBUYERON IGUALMENTE EN ESTE TRABAJO)

LIFE SCIENCES

Elsevier

Lugar: Amsterdam; Año: 2009 vol. 85 p. 444 - 449

0024-3205

Aims: Even though the presence of alpha 7 nicotinic receptor (nAChR) in lymphocytes has been demonstrated, its functional role still remains elusive. The aim of our study was to characterize alpha 7 nAChRs in human lymphocytes upon phytohemagglutinin (PHA) stimulation. Main methods: Lymphocytes were activated with the mitogen PHA. Alpha 7 nAChRs were studied by reverse transcription-polymerase chain reaction (RT-PCR), real time PCR, flow cytometry and confocal laser scanning microscopy. The effects of nicotinic drugs on PHA-induced proliferation was evaluated by the [3H]thymidine incorporation assay. Key findings:We show that the expression of functional alpha 7 receptors increases after PHA stimulation. The activation of peripheral lymphocytes by PHA increases 2.2-fold the alpha 7 subunit mRNA expression and 4-fold the binding of the antagonist alpha-bungarotoxin (a-BTX) with respect to the non activated lymphocytes. By  measuring the increase of the intracellular calcium in response to nicotine we determine that the alpha 7 receptors in lymphocytes are functional. Nicotinic drugs differentially modulate T cell activation.While nicotine tends to inhibit proliferative responses, the specific alpha 7 antagonists, such as alpha-BTX and methyllycaconitine, enhance cell division. Significance: This study reveals that the alpaha 7 receptor modulates lymphocyte activation and contributes to clarifying the role of the non neuronal cholinergic system in the immune response.