Role of A(2A) adenosine receptors in regulation of opsonized E. coli-induced macrophage function.
Adenosine is a biologically active molecule that is formed at sites of metabolic stress associated with trauma and inflammation, and its systemic level reaches high concentrations in sepsis. We have recently shown that inactivation of A(2A) adenosine receptors decreases bacterial burden as well as IL-10, IL-6, and MIP-2 production in mice that were made septic by cecal ligation and puncture (CLP). Macrophages are important in both elimination of pathogens and cytokine production in sepsis. Therefore, in the present study, we questioned whether macrophages are responsible for the decreased bacterial load and cytokine production in A(2A) receptor-inactivated septic mice. We showed that A(2A) KO and WT peritoneal macrophages obtained from septic animals were equally effective in phagocytosing opsonized E. coli. IL-10 production induced by opsonized E. coli was decreased in macrophages obtained from septic A(2A) KO mice as compared to WT counterparts. In contrast, the release of IL-6 and MIP-2 induced by opsonized E. coli was higher in septic A(2A) KO macrophages than WT macrophages. These results suggest that peritoneal macrophages are not responsible for the decreased bacterial load and diminished MIP-2 and IL-6 production that are observed in septic A(2A) KO mice. In contrast, peritoneal macrophages may contribute to the suppressive effect of A(2A) receptor inactivation on IL-10 production during sepsis.
Csóka
Balázs
B
Department of Surgery, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, University Heights, Newark, NJ, 07103, USA.
Németh
Zoltán H
ZH
Selmeczy
Zsolt
Z
Koscsó
Balázs
B
Pacher
Pál
P
Vizi
E Sylvester
ES
Deitch
Edwin A
EA
Haskó
György
G