TY - JOUR
T1 - Pneumolysin, a protein toxin of Streptococcus pneumoniae, induces nitric oxide production from macrophages
AU - Braun, Johann S.
AU - Novak, Rodger
AU - Gao, Geli
AU - Murray, Peter J.
AU - Shenep, Jerry L.
PY - 1999/8
Y1 - 1999/8
N2 - Nitric oxide (NO) production by inducible NO synthase (iNOS) during inflammation is an essential element of antimicrobial immunity but can also contribute to host-induced tissue damage. Under conditions of bacterial sepsis, large amounts of NO are produced, causing hypotension, a critical pathological feature of septic shock. In sepsis caused by gram-positive organisms, the bacterial factors contributing to host NO production are poorly characterized. We show that a soluble toxin of Streptococcus pneumoniae, pneumolysin (Pln), is a key component initiating NO production from macrophages. In contrast to wild-type bacteria, a mutant of S. pneumoniae lacking Pln failed to elicit NO production from murine macrophages. Purified recombinant Pln induced NO production at low concentrations and independently of exogenous gamma interferon (IFN-γ) priming of RAW 264.7 macrophages. However, IFN-γ was essential for Pln- induced NO production, since primary macrophages from mice lacking the IFN- γ receptor or interferon regulatory factor 1, a transcription factor essential for iNOS expression, failed to produce NO when stimulated with Pln. In addition, Pln acts as an agonist of tumor necrosis factor alpha and interleukin 6 production in macrophages. The properties of Pln, previously identified as a pore-forming hemolysin, also include a role as a general inflammatory agonist.
AB - Nitric oxide (NO) production by inducible NO synthase (iNOS) during inflammation is an essential element of antimicrobial immunity but can also contribute to host-induced tissue damage. Under conditions of bacterial sepsis, large amounts of NO are produced, causing hypotension, a critical pathological feature of septic shock. In sepsis caused by gram-positive organisms, the bacterial factors contributing to host NO production are poorly characterized. We show that a soluble toxin of Streptococcus pneumoniae, pneumolysin (Pln), is a key component initiating NO production from macrophages. In contrast to wild-type bacteria, a mutant of S. pneumoniae lacking Pln failed to elicit NO production from murine macrophages. Purified recombinant Pln induced NO production at low concentrations and independently of exogenous gamma interferon (IFN-γ) priming of RAW 264.7 macrophages. However, IFN-γ was essential for Pln- induced NO production, since primary macrophages from mice lacking the IFN- γ receptor or interferon regulatory factor 1, a transcription factor essential for iNOS expression, failed to produce NO when stimulated with Pln. In addition, Pln acts as an agonist of tumor necrosis factor alpha and interleukin 6 production in macrophages. The properties of Pln, previously identified as a pore-forming hemolysin, also include a role as a general inflammatory agonist.
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U2 - 10.1128/iai.67.8.3750-3756.1999
DO - 10.1128/iai.67.8.3750-3756.1999
M3 - Article
C2 - 10417133
AN - SCOPUS:0032768658
SN - 0019-9567
VL - 67
SP - 3750
EP - 3756
JO - Infection and Immunity
JF - Infection and Immunity
IS - 8
ER -