Physiological modulation od murine dendritic cells by cholinergic system: its impact in an in vivo model of allergic inflammation

GORI, MARÍA SOLEDAD; GEFFNER, JORGE; SABBIONE, FLORENCIA; SCORDO, WALTER; VANSULLI, SILVIA; JANCIC, CAROLINA; VERMEULEN, MÓNICA; GABRIELA, SALAMONE

Los Cocos

Congreso; 61 Reunión Anual de la Sociedad Argentina de Inmunología; 2013

Sociedad Argentina de Inmunología

Acetylcholine (ACh), the major neurotransmitter of cholinergic neurons, is synthesized by choline acetyltransferase from acetyl coenzyme A and choline. The functions of ACh are mediated through muscarinic and nicotinic receptors. In this work, we evaluated the murine Dendritic Cell (DC) physiological modulation by ACh. The DC were obtained from bone marrow precursors and were cultured during 10 days with J588-GM cell line supernatant. The DC were incubated with or without ACh (10-11M) during 24hs. We observed an increase in the expression of MHC class II, as well as in the production of TNF-alpha and MCP-1 in DC incubated with ACh (DC+ACh) compared with untreated DC (p<0.05). These effect were inhibited when cells were preincubated with Atropine (10-8M) (the antagonist of the muscarinic receptors). Moreover, the DC+ACh also increased the stimulation of the allogeneic T cell response (p< 0.05). Then, we investigated whether the course of an allergic response could be modulated by nasal instillation of DC+ACh in the beginning of allergic reaction in a well-defined model of ovalbumin (OVA)-induced allergic airway inflammation. After 15 days of nasal instillation of the DC, the lung were processed and phenotypically analyzed. We observed an increase in the CD11b+ and B220+ cells and a decrease in the CD11c+ cell population in mice instilled with DC+ACh compared with mice instilled with untreated DC (similar effects were observed when cells were instilled after the allergic reaction was established). Moreover, we perform a histopathology study of lung samples and we observed a pronounced infiltration of mononuclear cells accompanied with lost of the normal epithelial architecture of bronchus and decreased of alveolar lumen in the lung of the mice instilled with DC+ACh compared with untreated DC. In conclusion, the ACh acting on DC is able to induce an inflammatory response and it could be actively involved in the genesis of allergic inflammatory process.