Serum Levels Of Platelet-activating Factor Research Articles

New transcriptome and clinical findings of platelet-activating factor in chronic spontaneous urticaria: Pathogenic and treatment relevance.

The objective of the study was to assess the pathogenic and treatment relevance of Platelet Activating factor (PAF) in chronic spontaneous urticaria (CSU). The expression and cellular location of PAF receptor (PAFR) and serum levels of PAF and PAF acetylhydrolase (PAF-AH) in patients with moderate/severe CSU (n=45) and healthy controls (HCs, n=17) were studied. Skin samples from the active wheal (LS-CSU, 13 samples for qPCR and 33 for immunohistochemistry) and non-lesional skin (NLS-CSU, 13 samples) of CSU patients and HCs (13 samples and 5 for immunohistochemistry) were analyzed. Serum PAF and PAF-AH levels were measured by ELISA and compared between HC (10 samples) and CSU patients (25 samples) and, among them, between those refractory and non-refractory to second-generation H1 -antihistamines (sgAH). PAFR mRNA expression was significantly higher in LS-CSU versus HCs (p=0.014). PAFR positive staining in immunohistochemistry was mainly found in the epidermal basal layer in HCs, whereas it was broadly present along the epidermis in LS-CSU samples. Endothelial cells showed PAFR expression exclusively in LS-CSU and NLS-CSU samples. PAFR expression was observed in the nerves of HC, LS-CSU, and NLS-CSU samples. Double PAFR/CD43 expression showed that T-lymphocytes were the main cell type from the wheal inflammatory infiltrate expressing PAFR. A significantly lower PAF-AH/PAF ratio was observed in sgAH non-responders versus responders (6.1 vs. 12.6; p=0.049). Our study confirms that PAF is a mediator of wheal pathogenesis in CSU. The significantly lower PAF-AH/PAF ratio in sgAH non-responders vs responders suggests that PAF could be a potential biomarker of sgAH refractoriness.

Platelet-activating factor and antiphospholipid antibodies in recurrent implantation failure

Recurrent implantation failure (RIF) refers to cases in which women have had the failure of the embryo implantation after several in vitro fertilization (IVF). The success rate for IVF depends on many different factors. Implantation is a complex step in a successful pregnancy. Antiphospholipid antibodies (aPLs) and platelet-activating factor (PAF) can be considered as effective factors in the embryo implantation. The first purpose of this study is to compare the levels of aPLs and PAF among RIF and fertile control women. The second purpose is evaluating correlations between the blood levels of these factors in this two groups. The levels of twelve types of aPL and PAF in peripheral blood samples of RIF and fertile control women were checked with ELISA method. The results showed that levels of Anti Cardiolipin antibody IgG was above the normal level in 3% of RIF patients. This study examined for the first time the correlation between twelve types of aPLs and PAF in RIF and fertile women. The results of these correlations show that the serum levels of aPLs affects themselves and the serum levels of PAF. The correlation of aPLs levels and PAF levels was different in the two groups. Differences in the correlations of aPLs levels and PAF levels in two groups show that the equal changes in the level of variables examined can have different effects in RIF and the fertile control groups. It is suggested that the correlation between these variables be evaluated in other studies.

Ursodeoxycholic acid protects neonatal rats from necrotizing enterocolitis: a biochemical, histopathological, and immunohistochemical study

Background The pathophysiology of necrotizing enterocolitis (NEC) includes the massive production of endogenous cytokines with exaggerated activation of inflammatory pathways. Ursodeoxycholic acid (UDCA) has been used as an anti-inflammatory, antioxidant, and anti-apoptotic agent. We investigated the possible protective effects of UDCA in a neonatal rat pup model of NEC. Methods We randomly divided rat pups into three groups: a control group, a non-treated NEC group, and a UDCA-treated NEC group. We induced NEC by feeding formula enterally and via hypoxia/reoxygenation. Intestinal samples were collected for histopathological and immunohistochemical evaluation. Blood samples were taken for biochemical analyses. Results UDCA significantly reduced the extents of terminal ileal and jejunal injuries compared to the NEC group (p < .01), reduced Bax and caspase-3 immunoreactivities (both p < .01), and lowered serum levels of platelet-activating factor and intestinal fatty acid-binding protein (p < .01, p = .023, respectively). Conclusions In a rat model of NEC, UDCA protects against adverse intestinal histological, immunohistochemical, and biochemical changes. UDCA significantly reduces the effects of NEC on the rat pup intestine.

Serum platelet activating factor levels predicts refractoriness to antihistamine treatment in chronic spontaneous urticaria

This work was supported by a grant from the National Research Foundation of Korea (NRF) funded by the Korea government (MSIP) (NRF-2018R1A2B6006199) and a research grant from Ahn-Gook Pharmaceutical Co, Ltd, Seoul, Republic of Korea. Platelet activating factor (PAF) is one of the most potent phospholipid released from platelets as well as various inflammatory cells. PAF has been known to play a role in the regulation of immune responses and allergic inflammation. This study was aimed to compare circulating levels of PAF and PAF-acetylhydrolase (AH) which can catabolize PAF in patients with chronic spontaneous urticarial (CSU) and healthy controls (NC) and to investigate relationships of their levels and urticaria severity and therapeutic response. Serum PAF and PAF-AH levels were measured by ELISA in 283 CSU patients and 111 age- and sex-matched NCs. Urticaria severity was evaluated by urticaria activity score over 7 days (UAS7). Within 3 months after measuring PAF levels, patients whose urticaria was not controlled by antihistamine treatment were classified as histamine receptor 1 antagonist (H1RA) non-responders. Serum PAF levels were higher in CSU patients than in NCs (median 4368.9 [17.0–14768.3] vs. 3256.4 [27.1–13886.7] pg/ml, p = 0.015), while serum PAF-AH levels were lower in CSU patients (105.6 [2.6–296.4] vs. 125.7 [2.0–291.1] ng/ml, p = 0.001). H1RA non-responders had higher levels of PAF (3804.5 [17.0–11716.3] vs. 5426.3 [53.1–14768.3], p < 0.001) in their sera. A generalized linear model revealed that a higher UAS7 score (odds ratio 1.023) and a PAF level ≥ 5000 pg/ml (1.409) were significant predictors of a poor response to H1RA treatment. CSU patients, particularly those with H1RA refractoriness, showed significant increases in serum PAF levels and decreases in PAF-AH as compared with NCs. Therapies modulating PAF and PAF-AH levels could be effective in patients with CSU refractory to antihistamines.

Wheat‐dependent exercise‐induced anaphylaxis in Chinese people: a clinical research on 33 cases with antigenic analysis of wheat proteins

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a severe allergic condition in which wheat ingestion together followed by physical exercise induces anaphylaxis. For patients with WDEIA, omega-5 gliadin is considered to be one of the major allergens. To analyse the clinical features and allergen spectrum of WDEIA and to investigate the relationship between WDEIA and serum levels of platelet-activating factor (PAF), interleukin (IL)-9 and IL-33. Medical histories and conditions of WDEIA cases were collected and summarized, with allergen tests of wheat proteins measured at the same visit. Of the 33 patients enrolled, 13 also had serum levels of PAF, IL-9 and IL-33 measured. The healthy control (HC) group consisted of 13 healthy individuals, who also underwent both the wheat-protein allergen tests and the inflammatory-mediator tests. All patients experienced severe allergic reaction during exercise after wheat ingestion. Manifestations of WDEIA included facial oedema, generalized urticaria and respiratory symptoms. Unconsciousness was also observed in 21 cases. In the patient group, 57.6% were confirmed as hypersensitive to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), while 54.5% were allergic to omega-5 gliadin. PAF concentration was significantly higher in patients with WDEIA compared with HCs, whereas there was no significant difference in IL-9 or IL-33 between the two groups. WDEIA is a rare type of anaphylaxis. GAPDH and omega-5 gliadin may be the most common allergy-causing wheat proteins for Chinese people. PAF may be associated with the onset and development of WDEIA.

Levels of thrombin-activatable fibrinolysis inhibitor and platelet-activating factor in recurrent pregnancy loss patients

ObjectiveThe aim of this study was to investigate factors associated with thrombosis that may contribute to recurrent pregnancy loss (habitual abortion), specifically differences in serum levels of platelet-activating factor and thrombin-activatable fibrinolysis inhibitor (carboxypeptidase B2) between women with a history of recurrent miscarriage and those with no recurrent miscarriage history. Materials and methodsA case-controlled, prospective study design was adopted to compare women with a history of two or more first-trimester miscarriages (n = 42) with those with no history of recurrent miscarriage (n = 36). Participants were recruited from the Department of Obstetrics and Gynecology of Turgut Ozal University Hospital. Platelet-activating factor and thrombin-activatable fibrinolysis inhibitor levels in serum samples were measured by an enzyme-linked immunosorbent assay. ResultsPlatelet-activating factor levels were significantly (p = 0.018) higher in the recurrent miscarriage group. There was no difference in levels of thrombin-activatable fibrinolysis inhibitor expression between the groups. ConclusionPlatelet-activating factor is significantly higher in serum of patients with a history of recurrent miscarriage than in those without such a history, with potential implications for placental function and fetal growth, which could be relevant to miscarriage recurrence. Larger studies are indicated to further examine these findings.

Platelet-activating Factor Contributes to Bacillus anthracis Lethal Toxin-associated Damage

The lethal toxin (LeTx) of Bacillus anthracis plays a central role in the pathogenesis of anthrax-associated shock. Platelet-activating factor (PAF) is a potent lipid mediator that has been implicated in endotoxin-associated shock. In this study, we examined the contribution of PAF to the manifestations of lethal toxin challenge in WT mice. LeTx challenge resulted in transient increase in serum PAF levels and a concurrent decrease in PAF acetylhydrolase activity. Inhibition of PAF activity using PAF antagonists or toxin challenge of PAF receptor negative mice reversed or ameliorated many of the pathologic features of LeTx-induced damage, including changes in vascular permeability, hepatic necrosis, and cellular apoptosis. In contrast, PAF inhibition had minimal effects on cytokine levels. Findings from these studies support the continued study of PAF antagonists as potential adjunctive agents in the treatment of anthrax-associated shock.

Platelet-Activating Factor, PAF Acetylhydrolase, and Severe Anaphylaxis

Vadas P, Gold M, Perelman B, et al. N Engl J Med. 2008;358(1):28–35 PURPOSE OF THE STUDY. To characterize the roles of platelet-activating factor (PAF) and PAF acetylhydrolase, the enzyme that inactivates PAF, in humans. STUDY POPULATION. The population was a variety of pediatric and adult patients with different levels of allergic disease along with nonallergic controls. METHODS. Serum PAF levels and activity of PAF acetylhydrolase were measured 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 serum PAF levels were significantly higher in patients with anaphylaxis than in patients in the control groups 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. There was an inverse correlation between PAF levels and serum PAF acetylhydrolase activity. The proportion of patients with low PAF acetylhydrolase activity increased with the severity of anaphylaxis. Serum PAF acetylhydrolase activity was significantly lower in patients with fatal peanut anaphylaxis than in control patients. 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. REVIEWER COMMENTS. PAF is 1 of the proinflammatory mediators that are released systemically by the degranulation of mast cells and basophils. Although PAF is not the only mediator that plays a role in anaphylaxis, these results suggest that PAF is very important. Therefore, it may be useful to develop new pharmaceutical agents that block its actions. Additional research is also needed to determine if PAF and PAF acetylhydrolase measurements may be used as a screening tool to select patients at highest risk for fatal anaphylaxis.

Platelet-Activating Factor, PAF Acetylhydrolase, and Severe 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.

Periodontal parameters and platelet‐activating factor levels in serum and gingival crevicular fluid in a Chinese population

Platelet-activating factor (PAF) is a potent proinflammatory mediator and has been implicated in cardiovascular pathophysiology. The present clinical study assessed the relation between the severity of periodontal disease and PAF levels in gingival crevicular fluid (GCF) and serum. A total of 60 non-smoking subjects (21 periodontitis, 19 gingivitis patients and 20 healthy individuals) were included. Probing depth, attachment level, bleeding on probing, plaque index and sulphide levels were recorded at six sites of each tooth. GCF and blood samples were collected from all individuals, and PAF levels were investigated by enzyme-linked immunoabsorbent assay. The periodontitis group showed significantly higher PAF levels in the serum (329.3+/-287.3 pg/ml) and GCF (21.8+/-7.0 pg/sample) compared with the gingivitis group (138.0+/-77.9 pg/ml, 13.8+/-3.6 pg/sample) and with healthy controls (68.9+/-42.8 pg/ml, 2.4+/-2.7 pg/sample). The differences between patients and controls were statistically significant (p<or=0.05). Positive correlations were observed between PAF levels in GCF and serum and for PAF levels and clinical parameters. The present findings suggest a role of PAF in the pathogenesis of periodontitis. Based on the observed close correlation of GCF and serum PAF levels, future studies are warranted to test the hypothesis of a possible link between periodontitis and adverse systemic events mediated by PAF.

Clinical study on treatment of liver fibrosis of chronic hepatitis B patients with Ginkgo leaf

To study the anti-liver fibrosis effect of Ginkgo leaf in patients with chronic hepatitis B.Methods: Eighty-six patients with chronic hepatitis B were randomly divided into two groups with similar general condition. The 42 patients in the treated group were treated with Ginkgo leaf tablet (GLT), and the 44 patients in the control group were treated with Yiganling tablet. The treatment was conducted for 3 successive months in both groups. Changes in the histo-pathology of liver, serum levels of platelet activating factor (PAF), hyaluronic acid (HA), collagen type IV (C-IV), laminin (LN) and pro-collagen peptide type III (PC III) were observed before and after treatment. The markedly effective rate and the total effective rate in the treated group were 45.1% and 76.2% respectively, while in the control group the corresponding rates were 18. 2% and 43. 2%. Comparison between the two groups showed significant differenceP<0.01). Serum levels of PAF, HA, C-IV, LN and PC III were lowered significantly in the treated group after treatment. Compared with the corresponding parameters in the control group after treatment, the differences were all significant (P<0.01 orP<0.05). The pathological examination of liver showed improvement in both groups, the inflammation grade lowered in 10 patients (55. 6%) of the treated group and in 5 patients (35. 7%) of the control group, insignificant difference was shown between them. But in comparing the fibrosis staging lowering patients between the two groups, 12 patients (66. 7%) vs 3 patients (21.4%), the difference was significantP<0.05). Moreover, there were 4 patients in the control group with their fibrosis aggravated, while in the treated group, none was aggravatedP<0.05). Ginkgo leaf tablet has some liver protective and anti-liver fibrosis benefits.

Recombinant human platelet-activating factor acetylhydrolase reduces the frequency of diabetes in the diabetes-prone BB rat.

Platelet-activating factor (PAF) has been implicated in the development of type 1 diabetes. Our previous studies have suggested that PAF inhibitors reduce insulitis and the frequency of diabetes in BB rats. In this study, serum PAF levels were reduced to address the hypothesis that PAF is important for the development of insulitis. From the age of 35 days on, DP-BB rats were treated with human recombinant PAF acetylhydrolase (rPAF-AH), which efficiently inactivates PAF. Our data indicate that intraperitoneal injections of rPAF-AH reduce the incidence of diabetes in the DP-BB rat. Daily intraperitoneal injections of 6.0 mg/kg body wt rPAF-AH reduced the frequency of diabetes in saline-injected rats from 90% (27/30) to 57% (17/30) (P = 0.004). As found by morphometric analysis on pancreatic islets, DP-BB rats protected from diabetes had less severe degrees of insulitis in a dose-dependent manner. DP-BB rats protected by rPAF-AH also had a higher percentage of insulin-positive cells in pancreas sections compared with those from diabetic animals. We therefore speculated that the beta-cells were protected from insulitis by rPAF-AH.

The production of experimental cholecystitis by endotoxin

Acute acalculous cholecystitis (AAC) is a severe inflammatory disorder of the gallbladder. It occurs primarily in patients acutely ill from other disorders and is related to sepsis and shock. We previously found that platelet-activating factor (PAF), a phospholipid autacoid purported to be a mediator of the shock response, produced AAC. This study was performed to determine the effect of intravenous lipopolysaccharide (LPS) on feline gallbladders. Anesthetized cats underwent LPS administration with and without administration of a cyclooxygenase inhibitor and PAF antagonist. Gallbladder inflammation was evaluated by quantitation of luminal water transport and tissue myeloperoxidase levels. In an attempt to understand the mechanisms of the response, gallbladder perfusate and tissue prostanoid and PAF levels were quantitated as were serum PAF levels. LPS administration resulted in alteration of the normal absorptive pattern of the gallbladder mucosa to exsorption of fluid into the gallbladder lumen, increased tissue myeloperoxidase levels and increased serum PAF levels. This was associated with increased gallbladder tissue and perfusate prostanoid levels and increased perfusate PAF levels. Indomethacin prevented the pro-inflammatory changes in the gallbladder produced by LPS. The PAF antagonist, alprazolam, increased gallbladder prostanoid production when administered alone and with LPS. The administration of LPS resulted in the production of acute changes in the gallbladder consistent with cholecystitis. These changes being prevented by a cyclooxygenase inhibitor suggests that development of AAC may be related to the release of systemic and local pro-inflammatory substances.