Metabolism of platelet‐activating factor by blood platelets and plasma

Alam, Iftekhar; Smith, J B; Silver, Melvin J.

doi:10.1007/bf02535393

Cited by 57 publications

(20 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These requirements seem mandatory when trying to associate changes observed in ex vivo samples with changing clinical conditions. Metabolic conversion of PAF to alkyl-acyl-derivatives after interaction with the PAF-receptor has been reported in rabbit platelets (45), but not in human platelets (20,46,47). Our findings show a low conversion rate of PAF to alkyl-acyl-glycero-phosphocholine even after long periods ofincubation and this supports our method of isolating native PAF from ex vivo platelet samples.…”

Section: Resultssupporting

confidence: 84%

Occupancy of platelet receptors for platelet-activating factor in patients with septicemia.

Diez

Nieto²,

Fernandez-Gallardo³

et al. 1989

J. Clin. Invest.

View full text Add to dashboard Cite

The possible involvement of platelet-activating factor (PAF) in the pathogenesis of endotoxemia, was investigated by using a binding assay to patients' platelets, complemented with the extraction and chemical characterization of PAF obtained from patients' platelets. Platelets from 12 human volunteers had 281 +/- 63 freely accessible high affinity binding sites (PAF-receptors) per platelet; whereas this number was of 49 +/- 37 PAF-receptors per platelet, n = 14 samples, P less than 0.01, in a group of 13 patients with positive blood culture. A group of patients with respiratory or cardiovascular disturbances and negative blood culture had 253 +/- 74, accessible receptors per platelet (n = 19 samples from 16 patients, P less than 0.01 as compared to septic patients, which was not significantly different when compared to control individuals). Patients with sepsis possessed significant amounts of PAF associated to their platelets, whereas this mediator could not be isolated from platelets of patients with respiratory or cardiovascular disturbances and negative blood culture, nor from platelets of control individuals. PAF was also assayed in whole blood samples and found at high concentrations in sepsis patients. These data indicate that occupancy of PAF receptors in combination with high amounts of platelet-associated PAF, is a common finding in patients with sepsis.

show abstract

Section: Resultssupporting

confidence: 84%

Occupancy of platelet receptors for platelet-activating factor in patients with septicemia.

Diez

Nieto²,

Fernandez-Gallardo³

et al. 1989

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Diisopropyl fluorophosphate (1 mM) inhibited all the reactions of LCAT, although LAT-il appeared to be less sensitive than other reactions (results not shown). Diisopropyl fluorophosphate also inhibited the PAF-AH activities, in agreement with previous studies (5,19).…”

Section: Ambsractsupporting

confidence: 81%

Hydrolysis and transesterification of platelet-activating factor by lecithin-cholesterol acyltransferase.

Liu

Subbaiah

1994

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Purified lecithin-cholesterol acyltransferase (LCAT, EC 2.3.1.43) from human plasma was found to hydrolyze platelet-activating factor (PAF) to lyso-PAF and acetate. In addition, it catalyzed the transfer of the acetate group from PAF to lysophosphatidylcholine, forming lyso-PAF and a 1-acyl analog of PAF. In contrast to the cholesterol-esterification reaction carried out by the enzyme, the hydrolysis and transacetylation of PAF by LCAT did not require an apoprotein activator and were not inhibited by sulfhydryl inhibitors but were inhibited by serum albumin. When added to a proteoliposome substrate of LCAT or to whole plasma, PAF inhibited cholesterol esterification by LCAT competitively. PAF acetylhydrolase (EC 3.1.1.47), purified from human plasma, also catalyzed the transfer of acetate from PAF to lysophosphatidylcholine. However, the LCAT-catalyzed reactions of PAF were not due to contamination with PAF acetylhydrolase, since the ratio of acetyl transfer to acetyl hydrolysis was 3 times greater for LCAT, when compared with PAF acetylhydrolase under identical conditions. Furthermore, recombinant human LCAT secreted by baby hamster kidney cells also catalyzed the hydrolysis and transacetylation of PAF. These results demonstrate that LCAT can inactivate PAF in plasma by transacetylation and suggest that it may have a role in the metabolism of PAF, and possibly of oxidized phospholipids, in plasma.

show abstract

“…PAF acetylhydrolase production is known to occur in tissues (29,30) and blood cells (31) such as neutrophils, eosinophils, and platelets. Intracellular PAF acetylhydrolase plays an important role in metabolizing PAF within the cell (41)(42)(43)(44)(45). Some differences in enzyme properties between serum and intracellular acetylhydrolase, e.g., substrate specificity, have been reported (29,46).…”

Section: Resultsmentioning

confidence: 99%

Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children.

Miwa¹,

Miyake²,

Yamanaka³

et al. 1988

J. Clin. Invest.

283

116

View full text Add to dashboard Cite

Platelet-activating factor (PAF) acetylhydrolase has been recognized as an enzyme that inactivates PAF. We developed a convenient and reproducible method for determining human serum PAF acetyihydrolase activity. The assay was based on measurement of 1I4Clacetate produced from 1-O-alkyl-2-1'4C]-acetyl-sn-glycero-3-phosphocholine upon precipitation of the complex of radioactive substrate and albumin with TCA. The apparent Km value of PAF acetylhydrolase (near the physiological concentration of serum protein) was 1.5 X 10-4 M PAF. 32 subjects with serum PAF acetylhydrolase deficiency were found among 816 healthy Japanese adults. The low PAF acetylhydrolase activity in the deficient serum might not be due to the presence of enzyme inhibitor. Both the sensitivity to PAF and the metabolism of PAF in platelets from PAF acetylhydrolase-deficient subjects were almost the same as those of normal subjects. Deficiency in serum PAF acetylhydrolase appeared to be transmitted by autosomal recessive heredity among five Japanese families. Among healthy adults, healthy children, and asthmatic children, who were grouped into five classes on the basis of respiratory symptoms (remission, wheezy, mild, moderate, and severe groups), the probability of PAF acetylhydrolase deficiency was significantly higher in groups with severe symptoms (moderate and severe) (P < 0.01). These results suggest that deficiency of serum PAF acetylhydrolase might be one of the factors leading to severe respiratory symptoms in asthmatic children.

show abstract

Metabolism of platelet‐activating factor by blood platelets and plasma

Cited by 57 publications

References 20 publications

Occupancy of platelet receptors for platelet-activating factor in patients with septicemia.

Occupancy of platelet receptors for platelet-activating factor in patients with septicemia.

Hydrolysis and transesterification of platelet-activating factor by lecithin-cholesterol acyltransferase.

Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children.

Contact Info

Product

Resources

About