Resistance to endotoxin shock and reduced dissemination of gram-negative bacteria in CD14-deficient mice.
Endotoxin shock is the result of activation of the immune system by endotoxin/LPS, a component of Gram-negative bacteria. CD14, a GPI-anchored glycoprotein expressed strongly by monocyte/macrophages, is one of several receptors for endotoxin/LPS. The role of CD14 in bacterial-induced and LPS-induced shock was tested in CD14-deficient mice produced by gene targeting in embryonic stem cells. CD14-deficient mice were found to be highly resistant to shock induced by either live Gram-negative bacteria or LPS; however, at very high concentrations of LPS or bacteria, responses through non-CD14 receptors could be detected. Surprisingly, CD14-deficient mice also showed dramatically reduced levels of bacteremia, suggesting an unexpected role for CD14 in the dissemination of Gram-negative bacteria.
Haziot
A
A
Division of Molecular Medicine, North Shore University Hospital, Cornell University Medical College, Manhasset, New York 11030, USA.
Ferrero
E
E
Köntgen
F
F
Hijiya
N
N
Yamamoto
S
S
Silver
J
J
Stewart
C L
CL
Goyert
S M
SM
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004927:Escherichia coli Infections / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D018390:Gene Targeting; D018950:Lipopolysaccharide Receptors / Q000235:genetics* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D012772:Shock, Septic / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*
D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides