Platelet-Activating Factor, PAF Acetylhydrolase, and Severe Anaphylaxis
Platelet-activating factor (PAF) is an anaphylactic mediator that is degraded in the blood by the enzyme PAF acetylhydrolase. In this study, patients with anaphylactic reactions were found to have higher levels of circulating PAF and lower levels of PAF acetylhydrolase activity than were patients wi...
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| Published in | The New England journal of medicine Vol. 358; no. 1; pp. 28 - 35 |
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| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Boston, MA
Massachusetts Medical Society
03.01.2008
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Platelet-activating factor (PAF) is an anaphylactic mediator that is degraded in the blood by the enzyme PAF acetylhydrolase. In this study, patients with anaphylactic reactions were found to have higher levels of circulating PAF and lower levels of PAF acetylhydrolase activity than were patients without anaphylaxis. PAF-acetylhydrolase levels were low in patients who died as a result of an anaphylactic reaction to peanuts.
Patients with anaphylactic reactions were found to have higher levels of circulating platelet-activating factor (PAF) and lower levels of PAF acetylhydrolase activity than were patients without anaphylaxis.
Anaphylaxis is a rapid, potentially fatal, immediate hypersensitivity reaction characterized by laryngeal edema, bronchoconstriction, systemic hypotension, and vascular leakage.
1
Factors that predispose persons to anaphylaxis include age, atopy, asthma, mastocytosis, and activating mutations of mast cells.
2
–
4
Preformed and newly formed biochemical mediators, including histamine, tryptase, carboxypeptidase A, prostaglandin D
2
, leukotrienes, and platelet-activating factor (PAF), are released systemically during the degranulation of mast cells and basophils.
5
PAF is a proinflammatory phospholipid synthesized and secreted by mast cells, monocytes, and fixed tissue macrophages.
6
Circulating levels of PAF are, in part, controlled by the activity of PAF acetylhydrolase, which is . . . |
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| AbstractList | Platelet-activating factor (PAF) is an important mediator of anaphylaxis in animals, and interventions that block PAF prevent fatal anaphylaxis. The roles of PAF and PAF acetylhydrolase, the enzyme that inactivates PAF, in anaphylaxis in humans have not been reported.BACKGROUNDPlatelet-activating factor (PAF) is an important mediator of anaphylaxis in animals, and interventions that block PAF prevent fatal anaphylaxis. The roles of PAF and PAF acetylhydrolase, the enzyme that inactivates PAF, in anaphylaxis in humans have not been reported.We measured serum PAF levels and PAF acetylhydrolase activity in 41 patients with anaphylaxis and in 23 control patients. Serum PAF acetylhydrolase activity was also measured in 9 patients with peanut allergy who had fatal anaphylaxis and compared with that in 26 nonallergic pediatric control patients, 49 nonallergic adult control patients, 63 children with mild peanut allergy, 24 patients with nonfatal anaphylaxis, 10 children who died of nonanaphylactic causes, 15 children with life-threatening asthma, and 19 children with non-life-threatening asthma.METHODSWe measured serum PAF levels and PAF acetylhydrolase activity in 41 patients with anaphylaxis and in 23 control patients. Serum PAF acetylhydrolase activity was also measured in 9 patients with peanut allergy who had fatal anaphylaxis and compared with that in 26 nonallergic pediatric control patients, 49 nonallergic adult control patients, 63 children with mild peanut allergy, 24 patients with nonfatal anaphylaxis, 10 children who died of nonanaphylactic causes, 15 children with life-threatening asthma, and 19 children with non-life-threatening asthma.Mean (+/-SD) serum PAF levels were significantly higher in patients with anaphylaxis (805+/-595 pg per milliliter) than in patients in the control groups (127+/-104 pg per milliliter, P<0.001 after log transformation) and were correlated with the severity of anaphylaxis. The proportion of subjects with elevated PAF levels increased from 4% in the control groups to 20% in the group with grade 1 anaphylaxis, 71% in the group with grade 2 anaphylaxis, and 100% in the group with grade 3 anaphylaxis (P<0.001). There was an inverse correlation between PAF levels and PAF acetylhydrolase activity (P<0.001). The proportion of patients with low PAF acetylhydrolase values increased with the severity of anaphylaxis (P<0.001 for all comparisons). Serum PAF acetylhydrolase activity was significantly lower in patients with fatal peanut anaphylaxis than in control patients (P values <0.001 for all comparisons).RESULTSMean (+/-SD) serum PAF levels were significantly higher in patients with anaphylaxis (805+/-595 pg per milliliter) than in patients in the control groups (127+/-104 pg per milliliter, P<0.001 after log transformation) and were correlated with the severity of anaphylaxis. The proportion of subjects with elevated PAF levels increased from 4% in the control groups to 20% in the group with grade 1 anaphylaxis, 71% in the group with grade 2 anaphylaxis, and 100% in the group with grade 3 anaphylaxis (P<0.001). There was an inverse correlation between PAF levels and PAF acetylhydrolase activity (P<0.001). The proportion of patients with low PAF acetylhydrolase values increased with the severity of anaphylaxis (P<0.001 for all comparisons). Serum PAF acetylhydrolase activity was significantly lower in patients with fatal peanut anaphylaxis than in control patients (P values <0.001 for all comparisons).Serum PAF levels were directly correlated and serum PAF acetylhydrolase activity was inversely correlated with the severity of anaphylaxis. PAF acetylhydrolase activity was significantly lower in patients with fatal anaphylactic reactions to peanuts than in patients in any of the control groups. Failure of PAF acetylhydrolase to inactivate PAF may contribute to the severity of anaphylaxis.CONCLUSIONSSerum PAF levels were directly correlated and serum PAF acetylhydrolase activity was inversely correlated with the severity of anaphylaxis. PAF acetylhydrolase activity was significantly lower in patients with fatal anaphylactic reactions to peanuts than in patients in any of the control groups. Failure of PAF acetylhydrolase to inactivate PAF may contribute to the severity of anaphylaxis. Platelet-activating factor (PAF) is an important mediator of anaphylaxis in animals, and interventions that block PAF prevent fatal anaphylaxis. The roles of PAF and PAF acetylhydrolase, the enzyme that inactivates PAF, in anaphylaxis in humans have not been reported. We measured serum PAF levels and PAF acetylhydrolase activity in 41 patients with anaphylaxis and in 23 control patients. Serum PAF acetylhydrolase activity was also measured in 9 patients with peanut allergy who had fatal anaphylaxis and compared with that in 26 nonallergic pediatric control patients, 49 nonallergic adult control patients, 63 children with mild peanut allergy, 24 patients with nonfatal anaphylaxis, 10 children who died of nonanaphylactic causes, 15 children with life-threatening asthma, and 19 children with non-life-threatening asthma. Mean (+/-SD) serum PAF levels were significantly higher in patients with anaphylaxis (805+/-595 pg per milliliter) than in patients in the control groups (127+/-104 pg per milliliter, P<0.001 after log transformation) and were correlated with the severity of anaphylaxis. The proportion of subjects with elevated PAF levels increased from 4% in the control groups to 20% in the group with grade 1 anaphylaxis, 71% in the group with grade 2 anaphylaxis, and 100% in the group with grade 3 anaphylaxis (P<0.001). There was an inverse correlation between PAF levels and PAF acetylhydrolase activity (P<0.001). The proportion of patients with low PAF acetylhydrolase values increased with the severity of anaphylaxis (P<0.001 for all comparisons). Serum PAF acetylhydrolase activity was significantly lower in patients with fatal peanut anaphylaxis than in control patients (P values <0.001 for all comparisons). Serum PAF levels were directly correlated and serum PAF acetylhydrolase activity was inversely correlated with the severity of anaphylaxis. PAF acetylhydrolase activity was significantly lower in patients with fatal anaphylactic reactions to peanuts than in patients in any of the control groups. Failure of PAF acetylhydrolase to inactivate PAF may contribute to the severity of anaphylaxis. Platelet-activating factor (PAF) is an anaphylactic mediator that is degraded in the blood by the enzyme PAF acetylhydrolase. In this study, patients with anaphylactic reactions were found to have higher levels of circulating PAF and lower levels of PAF acetylhydrolase activity than were patients without anaphylaxis. PAF-acetylhydrolase levels were low in patients who died as a result of an anaphylactic reaction to peanuts. Patients with anaphylactic reactions were found to have higher levels of circulating platelet-activating factor (PAF) and lower levels of PAF acetylhydrolase activity than were patients without anaphylaxis. Anaphylaxis is a rapid, potentially fatal, immediate hypersensitivity reaction characterized by laryngeal edema, bronchoconstriction, systemic hypotension, and vascular leakage. 1 Factors that predispose persons to anaphylaxis include age, atopy, asthma, mastocytosis, and activating mutations of mast cells. 2 – 4 Preformed and newly formed biochemical mediators, including histamine, tryptase, carboxypeptidase A, prostaglandin D 2 , leukotrienes, and platelet-activating factor (PAF), are released systemically during the degranulation of mast cells and basophils. 5 PAF is a proinflammatory phospholipid synthesized and secreted by mast cells, monocytes, and fixed tissue macrophages. 6 Circulating levels of PAF are, in part, controlled by the activity of PAF acetylhydrolase, which is . . . Background: Platelet-activating factor (PAF) is an important mediator of anaphylaxis in animals, and interventions that block PAF prevent fatal anaphylaxis. The roles of PAF and PAF acetylhydrolase, the enzyme that inactivates PAF, in anaphylaxis in humans have not been reported. Methods: We measured serum PAF levels and PAF acetylhydrolase activity in 41 patients with anaphylaxis and in 23 control patients. Serum PAF acetylhydrolase activity was also measured in 9 patients with peanut allergy who had fatal anaphylaxis and compared with that in 26 nonallergic pediatric control patients, 49 nonallergic adult control patients, 63 children with mild peanut allergy, 24 patients with nonfatal anaphylaxis, 10 children who died of nonanaphylactic causes, 15 children with life-threatening asthma, and 19 children with non-life-threatening asthma. Results: Mean (+/- SD) serum PAF levels were significantly higher in patients with anaphylaxis (805 +/- 595 pg per milliliter) than in patients in the control groups (127 +/- 104 pg per milliliter, P < 0.001 after log transformation) and were correlated with the severity of anaphylaxis. The proportion of subjects with elevated PAF levels increased from 4% in the control groups to 20% in the group with grade 1 anaphylaxis, 71% in the group with grade 2 anaphylaxis, and 100% in the group with grade 3 anaphylaxis (P < 0.001). There was an inverse correlation between PAF levels and PAF acetylhydrolase activity (P < 0.001). The proportion of patients with low PAF acetylhydrolase values increased with the severity of anaphylaxis (P < 0.001 for all comparisons). Serum PAF acetylhydrolase activity was significantly lower in patients with fatal peanut anaphylaxis than in control patients (P values < 0.001 for all comparisons). Conclusions: Serum PAF levels were directly correlated and serum PAF acetylhydrolase activity was inversely correlated with the severity of anaphylaxis. PAF acetylhydrolase activity was significantly lower in patients with fatal anaphylactic reactions to peanuts than in patients in any of the control groups. Failure of PAF acetylhydrolase to inactivate PAF may contribute to the severity of anaphylaxis. [PUBLICATION ABSTRACT] |
| Author | Yeung, Jupiter Perelman, Boris Simons, F. Estelle R Vadas, Peter Gold, Milton Liss, Gary M Lack, Gideon Blyth, Thomas Simons, Keith J Cass, Dan |
| Author_xml | – sequence: 1 givenname: Peter surname: Vadas fullname: Vadas, Peter – sequence: 2 givenname: Milton surname: Gold fullname: Gold, Milton – sequence: 3 givenname: Boris surname: Perelman fullname: Perelman, Boris – sequence: 4 givenname: Gary M surname: Liss fullname: Liss, Gary M – sequence: 5 givenname: Gideon surname: Lack fullname: Lack, Gideon – sequence: 6 givenname: Thomas surname: Blyth fullname: Blyth, Thomas – sequence: 7 givenname: F. Estelle R surname: Simons fullname: Simons, F. Estelle R – sequence: 7 givenname: Keith J surname: Simons fullname: Simons, Keith J – sequence: 9 givenname: Dan surname: Cass fullname: Cass, Dan – sequence: 10 givenname: Jupiter surname: Yeung fullname: Yeung, Jupiter |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19971643$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/18172172$$D View this record in MEDLINE/PubMed |
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| Snippet | Platelet-activating factor (PAF) is an anaphylactic mediator that is degraded in the blood by the enzyme PAF acetylhydrolase. In this study, patients with... Platelet-activating factor (PAF) is an important mediator of anaphylaxis in animals, and interventions that block PAF prevent fatal anaphylaxis. The roles of... Background: Platelet-activating factor (PAF) is an important mediator of anaphylaxis in animals, and interventions that block PAF prevent fatal anaphylaxis.... |
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| SubjectTerms | 1-Alkyl-2-acetylglycerophosphocholine Esterase - blood Adolescent Adult Age Aged Allergies Anaphylaxis - blood Anaphylaxis - mortality Asthma - blood Asthma - immunology Biological and medical sciences Biomarkers - blood Blood pressure Case-Control Studies Child Child, Preschool Coma Drug Hypersensitivity - blood Epinephrine - pharmacology Epinephrine - therapeutic use Female General aspects Humans Injections, Intramuscular Insect Bites and Stings - blood Insect Bites and Stings - immunology Male Medical sciences Peanut Hypersensitivity - blood Platelet Activating Factor - analysis Prospective Studies Retrospective Studies Risk Factors Rodents Severity of Illness Index Teaching hospitals |
| Title | Platelet-Activating Factor, PAF Acetylhydrolase, and Severe Anaphylaxis |
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