Transgenic mice expressing human CD14 are hypersensitive to lipopolysaccharide.
In vitro studies have previously shown that the myelomonocytic differentiation antigen CD14 is a receptor for a complex consisting of lipopolysaccharide (LPS) and LPS-binding protein. To investigate the role of CD14 in vivo and its relationship to induction of LPS-induced endotoxin shock, transgenic mice expressing human CD14 were produced. These mice express human CD14 strongly on the surface of their monocytes, neutrophils, and Thy-1(+) lymphocytes and are hypersensitive to LPS, as evidenced by their increased susceptibility to endotoxin shock. These results document the importance of CD14 in vivo as a primary mediator of this lethal syndrome. Furthermore, these mice provide an important model for testing the therapeutic effects of agents directed specifically against the human, as opposed to the murine, CD14 protein in preventing LPS-induced endotoxin shock.
Ferrero
E
E
Department of Medicine, North Shore University Hospital/Cornell University Medical College, Manhasset, NY 11030.
Jiao
D
D
Tsuberi
B Z
BZ
Tesio
L
L
Rong
G W
GW
Haziot
A
A
Goyert
S M
SM
D000818:Animals; D015703:Antigens, CD / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D015214:Antigens, Differentiation, Myelomonocytic / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D004198:Disease Susceptibility / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides / Q000633:toxicity*; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology; D012016:Reference Values; D012772:Shock, Septic / Q000235:genetics / Q000276:immunology*
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase