The A2B adenosine receptor protects against inflammation and excessive vascular adhesion

J Clin Invest. 2006 Jul;116(7):1913-23. doi: 10.1172/JCI27933.


Adenosine has been described as playing a role in the control of inflammation, but it has not been certain which of its receptors mediate this effect. Here, we generated an A2B adenosine receptor-knockout/reporter gene-knock-in (A2BAR-knockout/reporter gene-knock-in) mouse model and showed receptor gene expression in the vasculature and macrophages, the ablation of which causes low-grade inflammation compared with age-, sex-, and strain-matched control mice. Augmentation of proinflammatory cytokines, such as TNF-alpha, and a consequent downregulation of IkappaB-alpha are the underlying mechanisms for an observed upregulation of adhesion molecules in the vasculature of these A2BAR-null mice. Intriguingly, leukocyte adhesion to the vasculature is significantly increased in the A2BAR-knockout mice. Exposure to an endotoxin results in augmented proinflammatory cytokine levels in A2BAR-null mice compared with control mice. Bone marrow transplantations indicated that bone marrow (and to a lesser extent vascular) A2BARs regulate these processes. Hence, we identify the A2BAR as a new critical regulator of inflammation and vascular adhesion primarily via signals from hematopoietic cells to the vasculature, focusing attention on the receptor as a therapeutic target.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood Vessels / cytology
  • Blood Vessels / physiology*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / physiology
  • Bone Marrow Transplantation
  • Cell Adhesion / physiology*
  • Cytokines / metabolism
  • E-Selectin / metabolism
  • Female
  • Genes, Reporter
  • Inflammation / metabolism*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Leukocyte Rolling
  • Mice
  • Mice, Knockout
  • P-Selectin / metabolism
  • Receptor, Adenosine A2B / genetics
  • Receptor, Adenosine A2B / metabolism*
  • Signal Transduction / physiology


  • Cytokines
  • E-Selectin
  • P-Selectin
  • Receptor, Adenosine A2B
  • Intercellular Adhesion Molecule-1