Synergistic action of nitric oxide release from murine macrophages caused by group B streptococcal cell wall and beta-hemolysin/cytolysin.
Group B streptococcus (GBS) is the leading cause of sepsis in neonates. Nitric oxide (NO) release plays a role in the hypotension that characterizes septic shock. It has been shown that GBS beta-hemolysin/cytolysin (beta-h/c) stimulates the transcription of inducible NO synthase (iNOS) in murine macrophages via intracellular pathways similar to those that mediate lipopolysaccharide-induced iNOS activation. Here, it is demonstrated that the GBS cell wall and beta-h/c act synergistically to induce iNOS in interferon (IFN)-gamma-primed [corrected] RAW 264.7 murine macrophages. In nonprimed macrophages, combined activation by the GBS cell wall plus beta-h/c is necessary to induce an NO response, which indicates that both virulence factors cooperate to substitute for the priming signal typically provided by IFN-gamma [corrected].
Ring
Axel
A
Department of Internal Medicine IV, Ruprecht-Karls-University, Heidelberg, Germany. axel_ring@med.uni-heidelberg.de
Depnering
Christiane
C
Pohl
Jürgen
J
Nizet
Victor
V
Shenep
Jerry L
JL
Stremmel
Wolfgang
W
D000818:Animals; D002473:Cell Wall / Q000737:chemistry*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006460:Hemolysin Proteins / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D013292:Streptococcus agalactiae / Q000737:chemistry*
D006460:Hemolysin Proteins; D009569:Nitric Oxide