Group B streptococcal beta-hemolysin induces nitric oxide production in murine macrophages

Group B streptococcus (GBS) is the leading cause of sepsis in neonates, Nit ric oxide (NO) release plays a role in the hypotension that characterizes s eptic shock. To examine the role of the GBS beta-hemolysin in NO production , the murine macrophage line RAW 264.7 was exposed to a wild-type (WT) GBS isolate and to hyperhemolytic (HH) and nonhemolytic (NH) transposon mutants derived from that isolate. After activation of macrophages by the WT strai n, the HH mutant, or cell-free extracts of beta-hemolysin, nitrite release into the supernatant increased >10-fold and inducible NO synthase (iNOS) le vels in cell lysates increased up to 10-fold compared with treatment with t he NH mutant or extracts from that mutant, Hemolysin-induced NO production was dependent on protein tyrosine kinases and NF-kappa B, but not on extrac ellular signal-related kinase-1/2-mitogen-activated kinases or protein kina se A. These results indicate that GBS beta-hemolysin induces murine macroph age iNOS via intracellular pathways similar to those that mediate lipopolys accharide-induced iNOS activation.