Infarct-sparing effect of adenosine A2B receptor agonist is primarily due to its action on splenic leukocytes via a PI3K/Akt/IL-10 pathway

Yingying Ni, Degang Liang, Yikui Tian, Irving L. Kron, Brent A. French, Zequan Yang

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: Adenosine A2B receptor (A 2B AR) agonist reduces myocardial reperfusion injury by acting on inflammatory cells. Recently, a cardiosplenic axis was shown to mediate the myocardial postischemic reperfusion injury. This study aimed to explore whether the infarct-squaring effect of A 2B AR agonist was primarily due to its action on splenic leukocytes. Methods: C57BL6 (wild type [WT]) mice underwent 40 min of left coronary artery occlusion followed by 60 min of reperfusion. A 2B AR knockout (KO) and interleukin (IL)-10KO mice served as donors for splenic leukocytes. Acute splenectomy was performed 30 min before ischemia. The acute splenic leukocyte adoptive transfer was performed by injecting 5 × 10 6 live splenic leukocytes into splenectomized mice. BAY 60-6583, an A 2B AR agonist, was injected by i.v. 15 min before ischemia. The infarct size (IS) was determined using 2,3,5-triphenyltetrazolium chloride and Phthalo blue staining. The expression of p-Akt and IL-10 was estimated by Western blotting. Immunofluorescence staining assessed the localization of IL-10 expression. Results: BAY 60-6583 reduced the myocardial IS in intact mice but failed to reduce the same in splenectomized mice, which had a smaller IS than intact mice. BAY 60-6583 reduced the IS in splenectomized mice with the acute transfer of WT splenic leukocytes; however, it did not protect the heart of splenectomized mice with the acute transfer of A 2B RKO splenic leukocytes. Furthermore, BAY 60-6583 increased the levels of p-Akt and IL-10 in the WT spleen. Moreover, it did not exert any protective effect in IL-10KO mice. Conclusions: A 2B AR activation before ischemia stimulated the IL-10 production in splenic leukocytes via a PI3K/Akt pathway, thereby exerting anti-inflammatory effects that limited the myocardial reperfusion injury.

Original languageEnglish (US)
Pages (from-to)442-449
Number of pages8
JournalJournal of Surgical Research
Volume232
DOIs
StatePublished - Dec 2018
Externally publishedYes

Keywords

  • Adenosine A2B receptor
  • Myocardial reperfusion injury
  • PI3K/Akt
  • Splenic leukocytes

ASJC Scopus subject areas

  • Surgery

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