Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma

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. J. Clin. Invest. 103:989-997

Protection against Oxidative Stress-induced Hepatic Injury by Intracellular Type II Platelet-activating Factor Acetylhydrolase by Metabolism of Oxidized Phospholipids in Vivo

“…These suppressive effects of plasma PAF-AH are thought to be due to its ability to hydrolyze PAF and PAF-like oxidized phospholipids. Four percent of the Japanese population lack plasma PAF-AH, and such a deficiency or decrease in plasma PAF-AH activity may be associated with severe asthma (31)(32)(33), atopy (32), stroke, and various cardiovascular diseases (34 -37). Intracellular type II PAF-AH (PAF-AH (II)) is a monomeric 40-kDa enzyme.…”

Functional impairment of two novel mutations detected in lipoprotein-associated phospholipase A2 (Lp-PLA2) deficiency patients

“…In some studies, a deficiency of plasma Lp-PLA2 was three times more common in children with severe bronchial asthma than in the general population, suggesting that Lp-PLA2 may play an important role in inflammatory and allergic responses (Stafforini et al 1999). Several other investigations have revealed that Lp-PLA2 mutations increase susceptibility to inflammatory and allergic diseases (Watson et al 1995;Tjoelker and Stafforini 2000).…”

“…About 80% of the Lp-PLA2 in plasma is bound to LDL via specific interaction between the C-terminus of apoB-100, the major constitutive protein of the LDL particle, and two domains of Lp-PLA2, one around tyrosine 205 and the other around tryptophan 115-leucine 116. The rest of the plasma Lp-PLA2 is bound to HDL and VLDL (Stafforini et al 1999;Kujiraoka et al 2003). The Lp-PLA2 enzyme is also known as platelet-activating factor (PAF) acetylhydrolase (PAF-AH), since one of its known functions is to deactivate PAF (Stafforini et al 1987a,b).…”

Clinical correlations of recent developments in the pathogenesis of atopic dermatitis

“…Third, the lack of functional serum PAF acetylhydrolase, which catalyzes hydrolysis of PAF and short-chained sn-2 GPC, has been linked to an exacerbated asthma phenotype in the approximately 4% of the Japanese population with homozygous mutations. 130 Finally, PAF stimulates the production of the anti-inflammatory cytokine IL-10 in epidermal and other cell types. 124 Of significance, the PAF receptor appears to be able to bind to ligands other than PAF.…”