SULFITE IS RELEASED BY HUMAN NEUTROPHILS IN RESPONSE TO STIMULATION WITH LIPOPOLYSACCHARIDE

Exposure to sulfite, a well-known air pollutant, induces inflammatory reactions characterized by neutrophil infiltration into the airways. U sing a simple and sensitive assay for sulfite concentration in biologi cal fluids, we demonstrate herein that human neutrophils released sign ificant amounts of sulfite (1.0 nmol/h/10(7) cells) in response to lip opolysaccharide (LPS), a major component of bacterial endotoxin, A lar ge proportion of the sulfite release by neutrophils Tvas dependent on inorganic sulfate contained in culture media, suggesting production vi a the sulfate reducing pathway in this response. We also show that glu cocorticoids and FK506 completely inhibit LPS-mediated sulfite release by neutrophils, Given the well-known antimicrobial activities of sulf ite, our results suggest that sulfite acts as a neutrophil mediator of host defense. A putative role of sulfite as an endogenous biological mediator is further underscored by the observation that in, vivo admin istration of LPS is associated with a marked increase in the serum con centration of sulfite in Wistar rats, Inhibition of sulfite release by immunosuppressive agents may contribute to increased susceptibility t o bacterial infection commonly associated with the administration of t hese drugs.