The responses of neutrophils to soluble and insoluble stimuli include aggregation, chemotaxis, lysosomal enzyme release, and the generation of active oxygen species such as superoxide anion. These processes, which have been described as stimulus-response coupling, can be influenced by ions, cyclic nucleotides, and metabolites of arachidonate (1) . In recent years, a role for adenosine has been described in the stimulus-response coupling of a variety of cells and tissues. Adenosine receptors and/or hormone like responses to adenosine have been reported in adipocytes, neurons, hepatocytes, smooth muscle cells, coronary arteries, and heart muscle (2-7). These responses have also been described in circulating cells of the blood, i.e., lymphocytes (8-10), macrophages (11), basophils (12), and mast cells (13).Adenosine in the presence of homocysteine thiolactone inhibits transmethylation reactions. These reactions are required for maintenance of high avidity receptors for the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (FMLP)t on murine macrophages. Pike and Snyderman (11) found that generation of superoxide anion by macrophages in response to FMLP was inhibited by adenosine. These studies suggested that adenosine might regulate stimulusresponse coupling in neutrophils as well. However, Marone et al. (14) were unable to demonstrate a significant effect of adenosine on the release of lysosomal enzyme (beta-glucuronidase) from human neutrophils stimulated by particle ingestion.We have therefore examined the role of adenosine as a modulator of superoxide anion generation, degranulation, and aggregation in human neutrophils exposed to soluble stimulants. We report that adenosine, at physiological concentrations, is a potent and specific regulator of neutrophil superoxide anion generation but exerts little or no effect on either degranulation or aggregation. Further, we demonstrate that this effect is independent of the cellular uptake of

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We have recently demonstrated that adenosine, acting via adenosine A2 receptors, inhibits generation of superoxide anions (O2-) by stimulated neutrophils. To determine the mechanism(s) by which adenosine inhibits O2- generation stimulated by the chemoattractant N-formylmethionylleucylphenylalanine (FMLP), we examined cyclic AMP (cAMP) concentrations, stimulated membrane depolarization and Ca2+ movements. Neither adenosine nor 5'-N-ethylcarboxamidoadenosine (NECA), the most potent agonist at adenosine A2 receptors, increases neutrophil cAMP content. However in the presence of the non-methylxanthine phosphodiesterase inhibitor, Ro-20-1724, both adenosine and NECA elicit a reversible increase in intracellular cAMP concentration. The chemoattractant FMLP also elicits an increment in the neutrophil cAMP content. NECA, in the presence of Ro-20-1724, synergistically enhances the increment in cAMP following stimulation by FMLP. However Ro-20-1724 does not potentiate the inhibition of O2- generation by NECA. Unlike other agents which increase neutrophil cAMP concentrations, NECA, even in the presence of a phosphodiesterase inhibitor, only trivially inhibits degranulation. We also found that adenosine markedly inhibits stimulated membrane depolarization but does not affect the stimulated increment in free ionized intracellular calcium. Moreover, inhibition by adenosine of O2- generation does not vary with the concentration of extracellular calcium. These results fulfil the last criterion for the demonstration of an A2 receptor on human neutrophils, and indicate that adenosine occupies an A2 receptor on neutrophils to raise intracellular cAMP in synergy with occupancy of the FMLP receptor. The results reported here also indicate that cAMP is not the second messenger for inhibition of O2- generation by adenosine and its analogues.

Non‐endemic Salmonella bacteremia tends to occur in patients with chronic disease. We reviewed all cases of Salmonella infection documented in adults at Bellevue Hospital during the years 1975–1982. Unexpectedly, the most frequent underlying disease found among bacteremic patients was systemic lupus erythematosus (SLE). Patients with SLE accounted for 6 of 30 Salmonella bacteremias as compared with 13 of 2,388 non‐Salmonella gram‐negative bacteremias. Salmonella was the single most frequent gram‐negative isolate from the blood of SLE patients. All lupus patients with Salmonella infection were bacteremic. In contrast, isolates from blood represented only 23% of all Salmonella infections documented in the non‐lupus population. Presentation was characterized by fever (>103°F) and abdominal pain. Four of the 6 patients were hypocomplementemic. All were receiving immunosuppressive therapy. We conclude that SLE patients in a municipal hospital setting are at increased risk for Salmonella sepsis. This should be considered when empiric antibiotic therapy is initiated.