PMID- 15271901
OWN - NLM
STAT- MEDLINE
DCOM- 20040820
LR  - 20181113
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 72
IP  - 8
DP  - 2004 Aug
TI  - Mouse susceptibility to anthrax lethal toxin is influenced by genetic factors in 
      addition to those controlling macrophage sensitivity.
PG  - 4439-47
AB  - Bacillus anthracis lethal toxin (LT) produces symptoms of anthrax in mice and 
      induces rapid lysis of macrophages (M phi) derived from certain inbred strains. 
      We used nine inbred strains and two inducible nitric oxide synthase (iNOS) 
      knockout C57BL/6J strains polymorphic for the LT M phi sensitivity Kif1C locus to 
      analyze the role of M phi sensitivity (to lysis) in LT-mediated cytokine 
      responses and lethality. LT-mediated induction of cytokines KC, MCP-1/JE, MIP-2, 
      eotaxin, and interleukin-1 beta occurred only in mice having LT-sensitive M phi. 
      However, while iNOS knockout C57BL/6J mice having LT-sensitive M phi were much 
      more susceptible to LT than the knockout mice with LT-resistant M phi, a 
      comparison of susceptibilities to LT in the larger set of inbred mouse strains 
      showed a lack of correlation between M phi sensitivity and animal susceptibility 
      to toxin. For example, C3H/HeJ mice, harboring LT-sensitive M phi and having the 
      associated LT-mediated cytokine response, were more resistant than mice with 
      LT-resistant M phi and no cytokine burst. Toll-like receptor 4 (Tlr4)-deficient, 
      lipopolysaccharide-nonresponsive mice were not more resistant to LT. We also 
      found that CAST/Ei mice are uniquely sensitive to LT and may provide an 
      economical bioassay for toxin-directed therapeutics. The data indicate that while 
      the cytokine response to LT in mice requires M phi lysis and while M phi 
      sensitivity in the C57BL/6J background is sufficient for BALB/cJ-like mortality 
      of that strain, the contribution of M phi sensitivity and cytokine response to 
      animal susceptibility to LT differs among other inbred strains. Thus, LT-mediated 
      lethality in mice is influenced by genetic factors in addition to those 
      controlling M phi lysis and cytokine response and is independent of Tlr4 
      function.
FAU - Moayeri, Mahtab
AU  - Moayeri M
AD  - Microbial Pathogenesis Section, National Institute of Allergy and Infectious 
      Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
FAU - Martinez, Nathaniel W
AU  - Martinez NW
FAU - Wiggins, Jason
AU  - Wiggins J
FAU - Young, Howard A
AU  - Young HA
FAU - Leppla, Stephen H
AU  - Leppla SH
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Toxins)
RN  - 0 (anthrax toxin)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
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  - Anthrax/genetics/*mortality
MH  - Antigens, Bacterial/immunology/*toxicity
MH  - Bacillus anthracis/*pathogenicity
MH  - Bacterial Toxins/immunology/*toxicity
MH  - Disease Susceptibility
MH  - *Genetic Predisposition to Disease
MH  - Macrophages, Peritoneal/*drug effects/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred Strains
MH  - Mice, Knockout
MH  - Nitric Oxide Synthase/genetics
MH  - Nitric Oxide Synthase Type II
PMC - PMC470648
EDAT- 2004/07/24 05:00
MHDA- 2004/08/21 05:00
PMCR- 2004/08/01
CRDT- 2004/07/24 05:00
PHST- 2004/07/24 05:00 [pubmed]
PHST- 2004/08/21 05:00 [medline]
PHST- 2004/07/24 05:00 [entrez]
PHST- 2004/08/01 00:00 [pmc-release]
AID - 72/8/4439 [pii]
AID - 0280-04 [pii]
AID - 10.1128/IAI.72.8.4439-4447.2004 [doi]
PST - ppublish
SO  - Infect Immun. 2004 Aug;72(8):4439-47. doi: 10.1128/IAI.72.8.4439-4447.2004.