Impaired anaphylactic responses with intact sensitivity to endotoxin in mice lacking a platelet-activating factor receptor.
Platelet-activating factor (PAF) is a potent phospholipid mediator with diverse biological activities in addition to its well-known ability to stimulate platelet aggregation. Pharmacologic studies had suggested a role for PAF in pregnancy, neuronal cell migration, anaphylaxis, and endotoxic shock. Here we show that disruption of the PAF receptor gene in mice caused a marked reduction in systemic anaphylactic symptoms. Unexpectedly, however, the PAF receptor-deficient mice developed normally, were fertile, and remained sensitive to bacterial endotoxin. These mutant mice clearly show that PAF plays a dominant role in eliciting anaphylaxis, but that it is not essential for reproduction, brain development, or endotoxic shock.
Ishii
S
S
Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Tokyo 113, Japan.
Kuwaki
T
T
Nagase
T
T
Maki
K
K
Tashiro
F
F
Sunaga
S
S
Cao
W H
WH
Kume
K
K
Fukuchi
Y
Y
Ikuta
K
K
Miyazaki
J
J
Kumada
M
M
Shimizu
T
T
D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D018390:Gene Targeting; D006321:Heart / Q000502:physiology; D006706:Homeostasis; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D051379:Mice; D010980:Platelet Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012098:Reproduction; D012772:Shock, Septic / Q000276:immunology
D008070:Lipopolysaccharides; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor