PMID- 17172979
OWN - NLM
STAT- MEDLINE
DCOM- 20071005
LR  - 20061218
IS  - 1073-2322 (Print)
IS  - 1073-2322 (Linking)
VI  - 27
IP  - 1
DP  - 2007 Jan
TI  - Elucidation of toll-like receptor and adapter protein signaling in vascular 
      dysfunction induced by gram-positive Staphylococcus aureus or gram-negative 
      Escherichia coli.
PG  - 40-7
AB  - Pathogens contain specific pathogen-associated molecular patterns, which activate 
      pattern recognition receptors of the innate immune system such as Toll-like 
      receptors (TLRs). Although there is a clear evidence of how macrophages sense 
      pathogens, we know less about such processes in vessels. This is critical to 
      understand because activation of vascular cells and the subsequent induction of 
      inflammatory genes by bacteria are crucial events in the development of septic 
      shock. In the current study we have used genetically modified mice to investigate 
      the role of TLRs, adapter proteins, tumor necrosis factor alpha (TNFalpha), and 
      nitric oxide synthase II (NOSII) in vascular dysfunction induced by Gram-positive 
      (Staphylococcus aureus) or Gram-negative (Escherichia coli) bacteria. Our data 
      show that Gram-positive S. aureus or Gram-negative E. coli causes vascular 
      dysfunction via the induction of NOSII. For S. aureus, this process requires 
      TLR2, TLR6, myeloid differentiation factor 88 (MyD88) adapter-like, MyD88, and 
      TNF, but not TLR4 or TLR1. Vascular dysfunction induced by E. coli requires TLR4 
      but has no requirement for TLR2, TLR1, TLR6, or TNF, and a partial but incomplete 
      requirement of MyD88 and TIR domain-containing adapter inducing interferon-beta. 
      Staphylococcus aureus induced NOSII protein expression in vascular smooth muscle 
      cells but not in macrophages, whereas E. coli induced NOSII in both cell types. 
      Our data are the first to establish the definitive roles of specific TLRs in the 
      sensing of Gram-positive and Gram-negative bacteria by vessels and demonstrate 
      that macrophages and blood vessels may differ in their response to pathogens.
FAU - Cartwright, Neil
AU  - Cartwright N
AD  - Department of Critical Care, National Heart and Lung Institute, Imperial College, 
      London, UK.
FAU - McMaster, Shaun K
AU  - McMaster SK
FAU - Sorrentino, Rosalinda
AU  - Sorrentino R
FAU - Paul-Clark, Mark
AU  - Paul-Clark M
FAU - Sriskandan, Shiranee
AU  - Sriskandan S
FAU - Ryffel, Bernhard
AU  - Ryffel B
FAU - Quesniaux, Valerie F J
AU  - Quesniaux VF
FAU - Evans, Timothy W
AU  - Evans TW
FAU - Mitchell, Jane A
AU  - Mitchell JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Toll-Like Receptors)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Escherichia coli/*physiology
MH  - Macrophages/enzymology
MH  - Mice
MH  - Mice, Knockout
MH  - Muscle, Smooth, Vascular/enzymology
MH  - Myocytes, Smooth Muscle/enzymology
MH  - Nitric Oxide Synthase Type II/biosynthesis/genetics
MH  - Rats
MH  - Signal Transduction/*physiology
MH  - Staphylococcus aureus/*physiology
MH  - Toll-Like Receptors/*physiology
MH  - Vascular Diseases/microbiology/*pathology
EDAT- 2006/12/19 09:00
MHDA- 2007/10/06 09:00
CRDT- 2006/12/19 09:00
PHST- 2006/12/19 09:00 [pubmed]
PHST- 2007/10/06 09:00 [medline]
PHST- 2006/12/19 09:00 [entrez]
AID - 00024382-200701000-00008 [pii]
AID - 10.1097/01.shk.0000235127.59492.db [doi]
PST - ppublish
SO  - Shock. 2007 Jan;27(1):40-7. doi: 10.1097/01.shk.0000235127.59492.db.