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Adenosine derived from Staphylococcus aureus-engulfed macrophages functions as a potent stimulant for the induction of inflammatory cytokines in mast cells

  • Ma, Ying Jie (National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University) ;
  • Kim, Chan-Hee (National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University) ;
  • Ryu, Kyoung-Hwa (National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University) ;
  • Kim, Min-Su (National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University) ;
  • So, Young-In (National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University) ;
  • Lee, Kong-Joo (Center for Cell Signaling Research, Division of Molecular Life Sciences and College of Pharmacy, Ewha Womans University) ;
  • Garred, Peter (Department of Clinical Immunology Sect. 7631, Rigshospitalet, University of Copenhagen) ;
  • Lee, Bok-Luel (National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University)
  • Received : 2011.03.02
  • Accepted : 2011.03.04
  • Published : 2011.05.31

Abstract

In this study, we attempted to isolate novel mast cell-stimulating molecules from Staphylococcus aureus. Water-soluble extract of S. aureus cell lysate strongly induced human interleukin-8 in human mast cell line-1 and mouse interleukin-6 in mouse bone marrow-derived mast cells. The active molecule was purified to homogeneity through a $C_{18}$ reverse phase HPLC column. By determination of its structure by MALDITOF and $^1H$- and $^{13}C$-NMR, adenosine was revealed to be responsible for the observed cytokine induction activities. Further studies using 8-sulfophenyl theophylline, a selective adenosine receptor blocker, verified that purified adenosine can induce interleukin-8 production via adenosine receptors on mast cells. Moreover, adenosine was purified from S. aureus-engulfed RAW264.7 cells, a murine macrophage cell line, used to induce phagocytosis of S. aureus. These results show a novel view of the source of exogenous adenosine in vivo and provide a mechanistic link between inflammatory disease and bacterial infection.

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