Platelet‐activating factor acetylhydrolase: A biomarker in Hymenoptera venom allergy?

Bilò, Maria Beatrice; Corsi, Alice; Martini, Matteo; Danieli, Maria Giovanna; Alia, Sonila; Paolo, A. Di; Moroncini, Gianluca; Vignini, Arianna

doi:10.1111/all.15161

Cited by 6 publications

(8 citation statements)

References 7 publications

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“…They found PAF‐AH activity was significantly lower in HVA than in healthy people 83 . Most recently, Bilo et al 84 reported serum PAF‐AH levels had no correlation with the severity of reaction observed in their HVA patients. They again confirmed that compared to healthy controls, PAF‐AH was significantly lower in HVA patients ( p < 0.001), and they also found PAF‐AH was lower than controls in asthma patients ( p = 0.001) and patients with rhinitis ( p = 0.014).…”

Section: Adult and Pediatric Data Of Paf/paf‐ah In Various Disease St...mentioning

confidence: 95%

“…Allergic/urticarial Anaphylaxis 23 High PAF and low PAF-AH at time of anaphylaxis associated with severe (vs. less mild or moderate) anaphylaxis 6 Low PAF-AH associated with fatal anaphylaxis 6 Low basal PAF-AH associated with severe anaphylaxis from Hymenoptera venom 82 PAF-AH was lower in adults with hymenoptera venom allergy than controls 83,84 PAF-AH was lower in children with severe anaphylaxis than mild-moderate 18 and was not altered from basal levels during anaphylaxis Transcriptional activity of the PAF-AH gene was lower in children with moderate anaphylaxis than in mild anaphylaxis or other controls 85 Allergic rhinitis 86 PAF elevated at baseline and after allergen nasal challenges Chronic urticaria 87 PAF levels elevated and PAF-AH decreased in patients refractory to antihistamines versus normal healthy controls…”

Section: Condition Detailsmentioning

confidence: 99%

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Platelet Activating Factor (PAF): A Mediator of Inflammation

et al. 2022

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Platelet-activating factor (PAF) is a phospholipid-derived mediator with an established role in multiple inflammatory states. PAF is synthesized and secreted by multiple cell types and is then rapidly hydrolyzed and degraded to an inactive metabolite, lyso-PAF, by the enzyme PAF acetylhydrolase. In addition to its role in platelet aggregation and activation, PAF contributes to allergic and nonallergic inflammatory diseases such as anaphylaxis, sepsis, cardiovascular disease, neurological disease, and malignancy as demonstrated in multiple animal models and, increasingly, in human disease states. Recent research has demonstrated the importance of the PAF pathway in multiple conditions including the prediction of severe pediatric anaphylaxis, effects on blood-brain barrier permeability, effects on reproduction, ocular diseases, and further understanding of its role in cardiovascular risk. Investigation of PAF as both a biomarker and a therapeutic target continues because of the need for directed management of inflammation. Collectively, studies have shown that therapies focused on the PAF pathway have the potential to provide targeted and effective treatments for multiple inflammatory conditions.

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Section: Adult and Pediatric Data Of Paf/paf‐ah In Various Disease St...mentioning

confidence: 95%

Section: Condition Detailsmentioning

confidence: 99%

Platelet Activating Factor (PAF): A Mediator of Inflammation

et al. 2022

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“…PAF is a potent proinflammatory mediator involved in the pathophysiology of several allergic diseases, including asthma and anaphylaxis 10 . PAF is biosynthesized by two distinct pathways: a remodeling or de novo pathway 23–26 .…”

Section: Discussionmentioning

confidence: 99%

“…PAF is known to be involved in the pathogenesis of anaphylaxis, depending on the stimuli 2,3 . PAF acts by binding to its specific PAF receptor and is rapidly inactivated and eliminated by PAF acetylhydrolase (PAF‐AH) in the circulation (the half‐life time of PAF: 3–13 min) 7,9,10 . Moreover, serum PAF levels are significantly higher in anaphylactic patients than in control patients and inversely correlate with PAF‐AH activity 11 .…”

Section: Introductionmentioning

confidence: 99%

Biotinylated peptides substituted with D‐amino acids with high stability as anti‐anaphylactic agents targeting platelet‐activating factor

Sato

Fukase

Ebina

2022

Journal of Peptide Science

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Platelet‐activating factor (PAF) is an important lipid mediator of anaphylaxis and therefore can be an anti‐anaphylactic agent target. Recently, we reported that several synthetic biotinylated peptides containing a Tyr‐Lys‐Asp‐Gly sequence markedly inhibited the bioactivities of PAF in vitro and in vivo; it also inhibited anaphylactic reactions such as hypothermia, hypotension, and vascular permeability in vivo. Here, we report the anti‐anaphylactic effects of three biotinylated heptapeptides (peptide 1: H‐Lys(biotinyl)‐Trp‐Tyr‐Lys‐Asp‐Gly‐Asp‐OH, peptide 2: H‐D‐Lys(biotinyl)‐Trp‐Tyr‐Lys‐Asp‐Gly‐Asp‐OH, and peptide 3: H‐D‐Lys(biotinyl)‐Trp‐Tyr‐Lys‐Asp‐Gly‐D‐Asp‐OH). The experiment using tryptophan fluorescence spectroscopy showed that the interaction of peptides 2 and 3 with PAF was larger than that of peptide 1. Experiments using a rat model of hind paw edema showed that peptides 1, 3, and 2 inhibited PAF‐induced edema by 67.9%, 69.3%, and 79.3%, respectively. In a mouse model of anaphylaxis, both peptides 2 and 3 showed inhibitory effects on anaphylactic hypothermia, whereas peptide 1 did not. Furthermore, experiments involving in vitro rat plasma stability of peptides showed that both peptides 3 and 2 were more stable in plasma compared to peptide 1 (84.0%, 51.8%, and 0%, remained after 6 h, respectively). Our results suggest that both peptides 2 and 3 may show systemic and local inhibitory effects as anti‐anaphylactic agents targeting PAF.

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“…PAF stimulates mast cells 23 and eosinophils, 24–26 and has been implicated in allergic conditions 27 such as anaphylaxis, 28–30 chronic spontaneous urticaria (CSU), 31–33 immediate and late cutaneous reactions, 34 and rhinitis 35–39 . Elevated PAF levels were strongly associated with severe anaphylaxis, more so than histamine or tryptase 28 .…”

mentioning

confidence: 99%