Bronchial hyperreactivity, increased endotoxin lethality and melanocytic tumorigenesis in transgenic mice overexpressing platelet-activating factor receptor.
Although platelet-activating factor (PAF) has been shown to exert pleiotropic effects on isolated cells or tissues, controversy still exists as to whether it plays significant pathophysiological roles in vivo. To answer this question, we established transgenic mice over-expressing a guinea-pig PAF receptor (PAFR). The transgenic mice showed a bronchial hyperreactivity to methacholine and an increased mortality when exposed to bacterial endotoxin. An aberrant melanogenesis and proliferative abnormalities in the skin were also observed in the transgenic mice, some of which spontaneously bore melanocytic tumors in the dermis after aging. Thus, PAFR transgenic mice proved to be a useful model for studying the basic pathophysiology of bronchial asthma and endotoxin-induced death, and screening of therapeutics for these disorders. Furthermore, our findings provide new insights regarding the role of PAF in the morphogenesis of dermal tissues as well as the mitogenic activity of PAF and PAFR in vivo.
Ishii
S
S
Department of Biochemistry, Faculty of Medicine, The University of Tokyo, Japan.
Nagase
T
T
Tashiro
F
F
Ikuta
K
K
Sato
S
S
Waga
I
I
Kume
K
K
Miyazaki
J
J
Shimizu
T
T
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D004731:Endotoxins / Q000633:toxicity; D005260:Female; D005298:Fertility / Q000235:genetics; D006168:Guinea Pigs; D008297:Male; D008546:Melanoma, Experimental / Q000209:etiology* / Q000235:genetics; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D010972:Platelet Activating Factor / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012744:Sex Ratio; D012772:Shock, Septic / Q000209:etiology / Q000401:mortality; D012878:Skin Neoplasms / Q000209:etiology* / Q000235:genetics
D016085:Bronchoconstrictor Agents; D004731:Endotoxins; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D016210:Methacholine Chloride; C044101:endotoxin, Escherichia coli