Prescott SM

References (4)

Title : Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma - Stafforini_1999_J.Clin.Invest_103_989
Author(s) : Stafforini DM , Numao T , Tsodikov A , Vaitkus D , Fukuda T , Watanabe N , Fueki N , McIntyre TM , Zimmerman GA , Makino S , Prescott SM
Ref : J Clinical Investigation , 103 :989 , 1999
Abstract : Asthma, a family of airway disorders characterized by airway inflammation, has an increasing incidence worldwide. Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma. Its proinflammatory actions are antagonized by PAF acetylhydrolase. A missense mutation (V279F) in the PAF acetylhydrolase gene results in the complete loss of activity, which occurs in 4% of the Japanese population. We asked if PAF acetylhydrolase deficiency correlates with the incidence and severity of asthma in Japan. We found that the prevalence of PAF acetylhydrolase deficiency is higher in Japanese asthmatics than healthy subjects and that the severity of this syndrome is highest in homozygous-deficient subjects. We conclude that the PAF acetylhydrolase gene is a modulating locus for the severity of asthma.
ESTHER : Stafforini_1999_J.Clin.Invest_103_989
PubMedSearch : Stafforini_1999_J.Clin.Invest_103_989
PubMedID: 10194471
Gene_locus related to this paper: human-PLA2G7

Title : Platelet-activating factor acetylhydrolases -
Author(s) : Stafforini DM , McIntyre TM , Zimmerman GA , Prescott SM
Ref : Journal of Biological Chemistry , 272 :17895 , 1997
PubMedID: 9218411
Gene_locus related to this paper: bovin-paf2 , human-PAFAH2

Title : Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase - Stafforini_1996_J.Clin.Invest_97_2784
Author(s) : Stafforini DM , Satoh K , Atkinson DL , Tjoelker LW , Eberhardt C , Yoshida H , Imaizumi T , Takamatsu S , Zimmerman GA , McIntyre TM , Gray PW , Prescott SM
Ref : J Clinical Investigation , 97 :2784 , 1996
Abstract : Deficiency of plasma platelet-activating factor (PAF) acetylhydrolase is an autosomal recessive syndrome that has been associated with severe asthma in Japanese children. Acquired deficiency has been described in several human diseases usually associated with severe inflammation. PAF acetylhydrolase catalyzes the degradation of PAF and related phospholipids, which have proinflammatory, allergic, and prothrombotic properties. Thus, a deficiency in the degradation of these lipids should increase the susceptibility to inflammatory and allergic disorders. Miwa et al. reported that PAF acetylhydrolase activity is absent in 4% of the Japanese population, which suggests that it could be a common factor in such disorders, but the molecular basis of the defect is unknown. We show that inherited deficiency of PAF acetylhydrolase is the result of a point mutation in exon 9 and that this mutation completely abolishes enzymatic activity. This mutation is the cause of the lack of enzymatic activity as expression in E. coli of a construct harboring the mutation results in an inactive protein. This mutation as a heterozygous trait is present in 27% in the Japanese population. This finding will allow rapid identification of subjects predisposed to severe asthma and other PAF-mediated disorders.
ESTHER : Stafforini_1996_J.Clin.Invest_97_2784
PubMedSearch : Stafforini_1996_J.Clin.Invest_97_2784
PubMedID: 8675689
Gene_locus related to this paper: human-PLA2G7

Title : Human plasma platelet-activating factor acetylhydrolase. Association with lipoprotein particles and role in the degradation of platelet-activating factor - Stafforini_1987_J.Biol.Chem_262_4215
Author(s) : Stafforini DM , McIntyre TM , Carter ME , Prescott SM
Ref : Journal of Biological Chemistry , 262 :4215 , 1987
Abstract : Platelet-activating factor (PAF) is a bioactive phospholipid (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) synthesized by a variety of mammalian cell types. PAF induces hypotension, and activates neutrophils and platelets, among other actions. Removal of the acetyl moiety abolishes biological activity, so this reaction may regulate the concentration of PAF and its physiological effects. We have studied the significance of this reaction, which is catalyzed in vitro by an acetylhydrolase present in mammalian plasma, blood cells, and tissues. We have shown that the plasma PAF-acetylhydrolase is responsible for the degradation of PAF in whole human blood and that alternate pathways for PAF degradation in plasma or blood cells are negligible. Human plasma PAF-acetylhydrolase is associated with low and high density lipoproteins (LDL and HDL with apoE). We have confirmed that the activity is a stable component of these particles by density gradient ultracentrifugation, chromatography on heparin-agarose, and immunoprecipitation. The LDL-associated activity accounts for most or all of the PAF degradation that occurs in plasma ex vivo, while the HDL-associated activity contributes little to this process. However, the two activities likely are due to a single protein since the HDL- and LDL-associated PAF-acetylhydrolase activities can transfer from one lipoprotein to the other. These transfer processes are pH-dependent and specific, since they only occur from LDL to a well characterized subclass of HDL (apoE-containing HDL) and vice versa. We discuss the equilibrium between the two particles and the role that this process may have in vivo.
ESTHER : Stafforini_1987_J.Biol.Chem_262_4215
PubMedSearch : Stafforini_1987_J.Biol.Chem_262_4215
PubMedID: 3549727