THE ROLE OF NITRIC-OXIDE IN EXPERIMENTAL MURINE SEPSIS DUE TO PYROGENIC EXOTOXIN A-PRODUCING STREPTOCOCCUS-PYOGENES

Nitric oxide (NO) produced by inducible NO synthase (iNOS) mediates hy potension in endotoxemia, In this study. NO induction by a toxin-produ cing Streptococcus pyogenes isolate, H250, and by recombinant streptoc occal pyrogenic exotoxin A (rSPEA) has been examined, both in vitro an d in vivo. Streptococcal supernatants, but not rSPEA, induce productio n of nitrite by marine macrophages when both are coincubated with gamm a interferon. Intraperitoneal injection of rSPEA did not cause signifi cant production of NO. However, an elevated level of nitrate in serum was detected in a model of streptococcal fasciitis due to live H250. i NOS was localized to Kupffer cells, hepatocytes, and renal tubular cel ls by immunostaining. Administration of a NOS inhibitor, N-G-monomethy l-L-arginine (L-NMMA), reduced peak concentrations of nitrate in serum but did not affect survival. NO is induced by H250, both in vitro and in vivo, mainly via SPEA-independent mechanisms, In this model, MOS i s expressed predominantly in the liver. Furthermore, in this model L-N MMA is not protective.