Moreover, it is also well known that the suppression selleckchem of phagocytic function of macrophage occurs by binding of adenosine to A2 receptors (Bours et al., 2006; Haskóet al., 2008; Kumar & Sharma, 2009). Both adenosine receptor types A2A and A2B are expressed in neutrophils, monocytes, macrophages, dendritic cells and T lymphocytes, and its EC50 for adenosine varies at 0.56–0.95 and 16.2–64.1 μM, respectively (Bours et al., 2006). Using adenosine
at the same range, at micromolar concentrations, we observed an inhibition of 50% in the percentage of infected macrophages (Fig. 6a and b). Although 5′-AMP, at the same concentration, did not have an effect in the interaction, 1 mM of 5′-AMP presented similar results to that observed with 100 μM of adenosine. This fact could be explained by the action of C. parapsilosis ecto-5′-nucleotidase activity in generating free adenosine to the medium. At 100 μM on of 5′-AMP, the rate of adenosine released could not achieve the effective concentration of free adenosine necessary to limit macrophage function, whereas at a higher concentration of 5′-AMP, the rate of extracellular adenosine could be more expressive. However, the presence of an ecto-5′-nucleotidase
activity on the external surface of macrophages BGB324 mouse (Edelson & Cohn, 1976a, b), able to hydrolyze 5′-AMP, could indicate that during the interaction assays, macrophages could be also responsible for adenosine generation contributing to reduction in the number of infected macrophages. Recently, our laboratory characterized ecto-ATPase activity on C. parapsilosis. The sequential dephosphorylation of ATP to adenosine was demonstrated by reverse-phase HPLC experiments, suggesting the presence of different enzymatic activities (ecto-ATPase, ecto-ADPase and ecto-5′-nucleotidase) on the surface of C. parapsilosis PRKD3 (Kiffer-Moreira et al., 2010). Ecto-ATPase was also associated with in vitro infectious processes because pretreatment with ATPase inhibitors led to a decrease of C. parapsilosis adhesion to host cells (Kiffer-Moreira et al., 2010). Colonization and infection with C.
parapsilosis are dependent upon the ability of the fungus to adhere to host cells and tissues, particularly mucosal surfaces (Trofa et al., 2008). The specific functions of ecto-ATPases and ecto-5′-nucleotidases are not fully known, but it has been demonstrated that they participate in many relevant biological processes (Zimmermann, 2000; Meyer-Fernandes, 2002). In C. parapsilosis, both enzymes play a role in the control of extracellular nucleotide concentrations and could have a role in limiting inflammation and immune responses from the host, favoring the establishment of infectious processes. The involvement of ecto-5′-nucleotidases and free adenosines during infections has been described for several microorganisms including protozoa (de Almeida Marques-da-Silva et al., 2008), bacteria (Thammavongsa et al.