Alpha 7 nicotinic acetylcholine receptor modulates lymphocyte activation

Aims: Even though the presence of α7 nicotinic receptor (nAChR) in lymphocytes has been demonstrated, its functional role still remains elusive. The aim of our study was to characterize α7 nAChRs in human lymphocytes upon phytohemagglutinin (PHA) stimulation. Main methods: Lymphocytes were activated with the mitogen PHA. α7 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 α7 receptors increases after PHA stimulation. The activation of peripheral lymphocytes by PHA increases 2.2-fold the α7 subunit mRNA expression and 4-fold the binding of the antagonist α-bungarotoxin (α-BTX) with respect to non activated lymphocytes. By measuring the increase of intracellular calcium in response to nicotine we determine that α7 receptors in lymphocytes are functional. Nicotinic drugs differentially modulate T cell activation. While nicotine tends to inhibit proliferative responses, specific α7 antagonists, such as α-BTX and methyllycaconitine, enhance cell division. Significance: This study reveals that the α7 receptor modulates lymphocyte activation and contributes to clarifying the role of the non neuronal cholinergic system in the immune response.Fil: de Rosa, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Dionisio, Leonardo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Agriello, Evangelina. Hospital Municipal General de Agudos Doctor José Penna; ArgentinaFil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Esandi, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentin