Increased plasma platelet-activating factor in children with acute asthmatic attacks and decreased in vivo and in vitro production of platelet-activating factor after immunotherapy

Hsieh, Kue‐Hsiung; Ng, Cheng-Koon

doi:10.1016/0091-6749(93)90271-g

Cited by 54 publications

(33 citation statements)

References 30 publications

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“…For example, blood PAF levels of asthmatic subjects with active symptoms were found to be significantly higher than those of patients during remission or healthy volunteers, suggesting that PAF may play a role in bronchial asthma (8,9). Increased levels of PAF also have been reported in children with acute asthmatic attacks (10). The desensitized state of human platelets has been used as an index of previous exposure to PAF and was shown to correlate with responsiveness to inhalation of specific allergens (11).…”

Section: Introductionmentioning

confidence: 99%

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

Stafforini¹,

Numao²,

Tsodikov³

et al. 1999

J. Clin. Invest.

119

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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

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Section: Introductionmentioning

confidence: 99%

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

Stafforini¹,

Numao²,

Tsodikov³

et al. 1999

J. Clin. Invest.

119

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“…Alterations in PAF acetylhydrolase activity have been reported in several disease states and can potentially contribute to the pathogenesis of these conditions (3). For example, acquired deficiency of PAF acetylhydrolase activity has been reported in patients with systemic lupus erythematosus and asthma (21,22), and increased levels of PAF have been reported in children with acute asthmatic attacks (23). In addition to these acquired deficiencies, Miwa et al described an inherited form of PAF acetylhydrolase deficiency (24).…”

Section: Introductionmentioning

confidence: 99%

Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase.

Stafforini¹,

Satoh²,

Atkinson³

et al. 1996

J. Clin. Invest.

256

184

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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. ( J. Clin. Invest. 1996. 97:2784-2791.)

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“…While PAF may not be the primary effector in the asthmatic response, it may act as a priming agent in a network of lipid mediators and cytokines involved in the chronic inflammatory process [5,19], and there is also evidence that systemic PAF concentrations are increased during acute asthma. A23187-stimulated granulocyte PAF production and plasma PAF levels are reported to be higher in children with asthma symptoms compared with asymptomatic or control children [16,17], and in patients with mild asthma, blood PAF levels were increased following allergen-induced bronchoconstriction [15] and during spontaneous exacerbations [18].…”

Section: Discussionmentioning

confidence: 99%

“…However, PAF has been detected in bronchoalveolar lavage fluid (BAL) from asthmatics [13], and allergen challenge has resulted in high levels of lyso-PAF in nasal fluids [14], and increased plasma PAF concentrations [15]. A number of recent studies have also suggested that systemic PAF concentrations may be increased in symptomatic asthmatic subjects [16][17][18]. Despite these observations, the interpretation of such measurements is complicated by factors such as the short half-life of PAF, the fact that lyso-PAF is both a precursor and metabolite of PAF, the likelihood that PAF acts mainly at localized sites of inflammation and that it may be rapidly metabolized and reincorporated by surrounding inflammatory cells [19].…”

mentioning

confidence: 99%

Lyso-PAF acetyltransferase activity in neutrophils of patients during acute asthma and after recovery

Misso

Gillon²,

Stewart³

et al. 1996

Eur Respir J

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L Ly ys so o--P PA AF F a ac ce et ty yl lt tr ra an ns sf fe er ra as se e a ac ct ti iv vi it ty y i in n n ne eu ut tr ro op ph hi il ls s o of f p pa at ti ie en nt ts s d du ur ri in ng g a ac cu ut te e a as st th hm ma a a an nd d a af ft te er r r re ec co ov ve er ry y ABSTRACT: The production of platelet-activating factor (PAF) by inflammatory cells is regulated by lyso-PAF acetyltransferase, and the activity of this enzyme is increased in neutrophils of stable asthmatic patients. The aim of this investigation was to determine whether acetyltransferase activity is further upregulated in asthmatic patients experiencing acute symptoms. A radioenzymatic assay was used to measure the enzymatic affinity constant (Km) and maximal enzymatic activity (Vmax) for acetyltransferase from unstimulated and Ca 2+ ionophore (A23187)-stimulated neutrophils from 16 patients with acute asthma, and the measurement was repeated at the time of discharge (n=9) and after recovery from the acute episode (n=13).During acute asthma, Km (median 93.8 (interquartile range 64.1-109.7) µM) was lower than that measured in nonasthmatic subjects in a previous study using identical methods (155.1 (122.2-179.9) µM; p=0.0001), and in 10 out of 13 acute patients Km for unstimulated neutrophils increased following recovery. In A23187-stimulated neutrophils, Km during acute asthma (84.3 (73.6-100.2) µM) and at discharge (83.9 (83.1-94.8) µM) were similar, but Km after recovery was increased (115.0 (95.6-119.5) µM; p=0.02). The change in Km following stimulation with A23187 was also significantly less during acute asthma than previously measured in nonasthmatic subjects (p=0.003). Although Vmax during acute asthma (12.9 (interquartile range 10.5-22.5) nmol·min -1 ·mg -1 protein) did not differ significantly from that at discharge (14.4 (12.3-20.4) nmol·min -1 ·mg -1 ) or after recovery (17.3 (12.3-18.4) nmol·min -1 ·mg -1 ), both median Km and Vmax tended to be lowest during acute asthma and increase at discharge and after recovery.An increase in lyso-PAF acetyltransferase activity alone may not account for increased systemic PAF concentrations during acute asthma. However, the reduction in the enzymatic affinity constant and its smaller change following in vitro stimulation suggest that alterations in the affinity of acetyltransferase for acetylcoenzyme A (CoA) and in the regulation of enzyme activity may be occurring during acute asthma.

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Increased plasma platelet-activating factor in children with acute asthmatic attacks and decreased in vivo and in vitro production of platelet-activating factor after immunotherapy

Cited by 54 publications

References 30 publications

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

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

Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase.

Lyso-PAF acetyltransferase activity in neutrophils of patients during acute asthma and after recovery

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