Adenosine is an Antiinflammatory Autocoid: Adenosine Receptor Occupancy Promotes Neutrophil Chemotaxis and Inhibits Superoxide Anion Generation

Abstract

While migrating to sites of infection or tissue injury neutrophils and other inflammatory cells are in close contact with tissue cells. Migrating neutrophils are under the influence of chemoattractants which may also stimulate the neutrophil to generate potentially toxic oxygen metabolites. We and, subsequently, others have shown that adenosine, a purine released by many tissues, inhibits superoxide anion generation and adherence to endothelium by activated neutrophils yet, paradoxically, promotes neutrophil chemotaxis (Roberts et al.1985; Skubitz et al.1988; Grinstein et al.1986; Schmeichel et al.1987; Cronstein et al.1983; Rose et al.1988; Cronstein et al.1987; Cronstein et al.1986; Cronstein et al.1985; Schrier et al.1986; Iannone et al.1985). These effects on neutrophil function, mediated through occupancy of specific neutrophil receptors for adenosine, are unlike those of any other physiologic modulator of neutrophil function. Even more surprisingly, we have found that adenosine and its analogues modulate chemotaxis at concentrations markedly lower than those required to inhibit superoxide anion generation, an observation which could be accounted for by the presence of two distinct neutrophil adenosine receptors.