G2a protects mice against sepsis by modulating Kupffer cell activation: Cooperativity with adenosine receptor 2B

Academic Article


  • G2A is a GPCR abundantly expressed in immune cells. G2A 2 / 2 mice showed higher lethality, higher plasma cytokines, and an impaired bacterial clearance in response to a murine model of sepsis (cecal ligation and puncture), which were blocked by GdCl 3 , an inhibitor of Kupffer cells. Antiā€“IL-10 Ab reversed the impaired bacterial clearance in G2A 2 / 2 mice. Indomethacin effectively blocked both the increased i.p. IL-10 levels and the impaired bacterial clearance, indicating that disturbed PG system is the proximal cause of these phenomena. Stimulation with LPS/C5a induced an increase in Escherichia coli phagocytosis and intracellular cAMP levels in G2A +/+ peritoneal macrophages but not G2A 2 / 2 cells, which showed more PGE 2 /nitrite release and intracellular reactive oxygen species levels. Heterologous coexpression of G2A and adenosine receptor type 2b (A2bAR) induced a synergistic increase in cAMP signaling in a ligand-independent manner, with the evidence of physical interaction of G2A with A2bAR. BAY 60-6583, a specific agonist for A2bAR, increased intracellular cAMP levels in Kupffer cells from G2A +/+ but not from G2A 2 / 2 mice. Both G2A and A2bAR were required for antiseptic action of lysophosphatidylcholine. These results show inappropriate activation of G2A 2 / 2 Kupffer cells to septic insults due to an impaired cAMP signaling possibly by lack of interaction with A2bAR.
  • Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 16391404
  • Author List

  • Li HM; Jang JH; Jung JS; Shin J; Park CO; Kim YJ; Ahn WG; Nam JS; Hong CW; Lee J
  • Start Page

  • 527
  • End Page

  • 538
  • Volume

  • 202
  • Issue

  • 2