CONICET | Buscador de Institutos y Recursos Humanos

Acetylcholine (ACh), the major neurotransmitter of cholinergic neurons, is synthesized by choline acetyltransferase from acetyl coenzyme A and choline. The functions of ACh are mediate through two different receptors, muscarinic and nicotinic. First, we evaluated the murine Dendritic Cell (DC) physiological modulation by ACh. For that, DC were obtained from bone marrow precurosrs and were cultured during 10 days with J588-GM cell line supernatant. Finally, DC were incubated with or without ACh (10-11M) during 24hs. We observed that ACh increases the expression of MHC class II, as well as the production of TNF-alpha and MCP-1 cytokines by DC respect to untreated DC (p<0.05). These effects were inhibited when the cells were pre-incubated with Atropine (10-8M) (an antagonist of muscarinic receptors). Moreover, the DC+ACh also increased the stimulation of the allogeneic response (p< 0.05). In a second approach, we investigated whether the course of allergic response could be modulated by nasal instillation of DC+ACh at the beguine of allergic reaction in a well-defined model of ovalbumin (OVA)-induced allergic airway inflammation. After 15 days of instillation, the lung were processed and phenotypically analyzed. We observed an increase in the CD11b+ and B220+ while decreased CD11c+ cell population in mice received DC+ACh respect mice instilled with DC untreated (similar effects were observed when the DC were instilled at established allergic reaction). Moreover, in mice instillated with DC+Ach; the histopathology analysis we showed a more pronounced infiltration of mononuclear cells accompanied with the lost of epithelial architecture of bronchus, more thickening of the walls and decreased in the alveolar lumen of the normal lung. In conclusion, the Ach acting on DC are able to induce an inflammatory response, probably mediated by muscarinic receptors, that affect the genesis of allergic inflammatory process.