Endogenous adenosine formation can regulate human neutrophil function.

Abstract

Neutrophils, in addition to their role in host defense, can cause injury to normal tissues during inflammatory processes. Oxygen radicals and secreted proteases, in particular, are responsible for some aspects of neutrophil-mediated injury to endothelial cells and cardiomyocytes. A variety of neutrophil functions, including adhesion and reactive oxygen species production, are inhibited by adenosine (Ado) (Cronstein, 1991 and Cronstein, et al., 1992). Furthermore, inhibition of neutrophil adhesion by adenosine regulating agents like acadesine and adenosine kinase (AK) inhibitors (Firestein, et al., 1994) appears to be mediated by Ado, since it is reversed by the addition of adenosine deaminase (ADA) or Ado receptor antagonists. Although Ado and adenine nucleotides can be released at inflammatory sites during platelet aggregation or from endothelial cells during ischemic stress conditions, little is known about Ado formation by human neutrophils. To determine if neutrophils can serve as an endogenous Ado source and thereby provide an autocrine stimulus, we evaluated purine metabolism and Ado formation in human neutrophils.