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. Author manuscript; available in PMC: 2013 Jun 1.
Published in final edited form as: Anesthesiology. 2012 Jun;116(6):1245–1257. doi: 10.1097/ALN.0b013e318255793c

Figure 7. Adora2b signaling in human PMNs.

Figure 7

(A, B) Human polymorphonuclear leukocytes (PMNs) were isolated from healthy individuals and activated using formyl-Met-Leu-Phe (fMLP 10 nM). Cells were either treated with a specific Adora2b antagonist (PSB 1115, 100 µM, a) or an Adora2b agonist (BAY 60–6583,1µM, b) or vehicle. Tumor necrosis factor-alpha (TNFα) release into the supernatant was measured by ELISA. Vehicle treatment of PMNs significantly increased TNFα with a maximal response after 30 and 60 min following activation (22.88 ± 4.0 pg/ml and 31.4 ± 5.4 pg/ml, respectively). (A) Pretreatment with an Adora2b antagonist enhances TNFα secretion significantly (24.8 ± 4.8, 42.3 ± 3.2, 48.6 ± 4.0 and 28 ± 4.6 pg/ml at 5, 30, 60, or 120 min, respectively). (B) Pretreatment with an Adora2b agonist significantly dampens TNFα release (7.89 ± 1.3, 10.70 ± 2.6, 15.9 ± 2.5 and 5.5 ± 0.9 pg/ml at 5, 30, 60, and 120 min, respectively; n = 5 per group). (C, D) Proposed role and potential therapeutic intervention: Cardiac ischemia reperfusion injury leads to PMN adhesion to the endothelial cells in the area at risk. (C) PMNs release TNFα, which further damages the myocardial tissue and enhances reperfusion injury. (D) Pharmacological treatment upon reperfusion using an Adora2b agonist activates A2B adenosine receptors on PMNs, which inhibits TNFα release and thereby protects the myocardium from further damage.