Sulfite is Generated from PAPS by Activated Neutrophils

We previously reported that neutrophils produce sulfite in response to stimulation with lipopolysaccharide, and sulfite production is dependent on inorganic sulfate contained in culture media. Microorganisms such as yeast assimilate sulfate, during which process sulfite is generated by reduction of 3′-phosphoadenosine 5′-phosphosulfate (PAPS), an activated sulfate donor. However, little is known about how sulfite is produced in mammalian cells. In the current study, we demonstrated that chlorate, a specific inhibitor for PAPS synthesis, significantly suppressed production of sulfite by activated neutrophils obtained from rat peritoneal cavity that had been injected with glycogen to induce inflammation. Addition of excess amounts of PAPS could partially overcome the inhibitory effect of chlorate. Moreover, sulfite production from PAPS was clearly demonstrated in the cytosolic fraction of activated neutrophils. These findings strongly suggest that sulfite is generated, at least in part, from PAPS by activated neutrophils.