Modulation of dendritic cell function by acetylcholine

GABRIELA SALAMONE, KAREN NAHMOD, MÓNICA VERMEULEN, DIEGO MARTINEZ, ANA CEBALLOS, JUAN SABATTE, MARÍA MARTA AMARAL, MARÍA EUGENIA ALVAREZ AND JORGE GEFFNER.

Córdoba Argentina

Congreso; ALAI ( VII Congreso Latinoamericano de Inmunología); 2005

ALAI ( VII Congreso Latinoamericano de Inmunología)

Acetylcholine (ACh), the major neurotransmitter of cholinergic neurons, is synthesized by choline acetyltransferase from acetyl coenzyme A and choline. ACh mediates its action through two different receptors, muscarinic and nicotinic. Here, we analyzed the impact of ACh on DC function. DC (90% purity) were differentiated from human monocytes cultured for 5 days in the presence of GM-CSF and IL-4. Expression of HLA-DR was evaluated by flow cytometry and the results expressed as the percentage of increase in the median fluorescence intensity. We found that exposure of DC to ACh (range 0.1-100 nM) significantly increased (p<0.05) the expression of HLA-DR in both, untreated and LPS-treated DC (1mg/ml, 24 h): % enhancement= 60-100%, and 30-80%, respectively, n=5). Interestingly, we also observed that DC treated for 24 h with neostigmine 20mM (an acetylcholinesterase inhibitor) or Iso-OMPA 10uM (a butyrylcholinesterase inhibitor) significantly increased (p<0.05) the expression of HLA-DR in either, untreated or LPS-treated DC (n=5). Finally, we found that the muscarinic receptor antagonist atropine (range 1-1000 nM, 24 h) did not modify the expression of HLA-DR in untreated DC but significantly increased (p< 0.05) its expression in LPS-treated DC. Our results suggest the existence of an autocrine/paracrine loop through which ACh modulate the function of DC.