Intracellular adenosine released from THP-1 differentiated human macrophages is involved in an autocrine control of Leishmania parasitic burden, mediated by adenosine A2A and A2B receptors.

Intracellular adenosine released from THP-1 differentiated human macrophages is involved in an autocrine control of Leishmania parasitic burden, mediated by adenosine A2A and A2B receptors. Eur J Pharmacol. 2020 Aug 25;:173504 Authors: Silva D, Moreira D, Cordeiro-da-Silva A, Quintas C, Gonçalves J, Fresco P Abstract Leishmania infected macrophages have conditions to produce adenosine. Despite its known immunosuppressive effects, no studies have yet established whether adenosine alter Leishmania parasitic burden upon macrophage infection. This work aimed at investigating whether endogenous adenosine exerts an autocrine modulation of macrophage response towards Leishmania infection, identifying its origin and potential pharmacological targets for visceral leishmaniasis (VL), using THP-1 differentiated macrophages. Adenosine deaminase treatment of infected THP-1 cells reduced the parasitic burden (29.1 ± 2.2%, P < 0.05). Adenosine A2A and A2B receptor subtypes expression was confirmed by RT-qPCR and by immunocytochemistry and their blockade with selective adenosine A2A and A2B antagonists reduced the parasitic burden [14.5 ± 3.1% (P < 0.05) and 12.3 ± 3.1% (P < 0.05), respectively; and 24.9 ± 2.8% (P < 0.05), by the combination of the two antagonists)], suggesting that adenosine A2 receptors are tonically activated in infected THP-1 differentiated macrophages. The tonic activation of a...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research