Serum Platelet-activating Factor Acetylhydrolase Activity Research Articles

Platelet-activating factor acetylhydrolase is a biomarker of severe anaphylaxis in children.

There is limited ability to predict the severity of allergic reactions in children. Data derived predominantly from adults have implicated the platelet-activating factor pathway as a potential contributor to severe anaphylaxis. In this study, we sought to prospectively assess involvement of key components of the platelet-activating factor pathway in pediatric patients with anaphylaxis. Forty-six pediatric patients (<18years) presenting with acute anaphylaxis were assessed. Anaphylaxis severity was graded and serum anaphylaxis markers were measured acutely and in 36 children who returned for follow-up >4weeks after their acute presentation. These markers were compared with pediatric laboratory reference sera. Severe anaphylaxis was experienced by 12/46 (26%) and mild-moderate anaphylaxis in 34/46 (74%) children. Platelet-activating factor acetylhydrolase (PAF-AH) activity was inversely associated with severe anaphylaxis: 9/12 children with severe anaphylaxis had reduced PAF-AH activity as compared with 14/34 with mild-moderate anaphylaxis (p < .05). Furthermore, 3/3 children who required intensive care had markedly reduced mean PAF-AH (nmol/ml/min) (13.73, 95%CI: 7.42-20.03) versus 20/23 who required ward/emergency department care (17.81, 95%CI: 16.80-18.83; p < .05). In children with anaphylaxis, PAF-AH during acute anaphylaxis was unchanged relative to the child's basal levels (mean, 17.26, 95%CI: 16.10-18.42 vs 17.50, 95%CI: 16.21-18.78, p = .63) and was lower than healthy pediatric controls (mean 19.21; 95%CI:18.21-20.21; p < .05). Decreased serum PAF-AH activity is a biomarker of severe anaphylaxis. Levels of this enzyme do not change from basal levels during acute anaphylaxis. Our results show that PAF-AH is a biomarker of anaphylaxis severity in children. This key regulatory enzyme may modulate susceptibility to severe anaphylaxis.

Serum platelet-activating factor acetylhydrolase and paraoxonase-1 activity in horses infected with Leptospira spp

The aim of the study was to investigate the effect of infection with Leptospira spp. in horses on activities of platelet-activating factor acetylhydrolase (PAF-AH) and paraoxonase-1 (PON1) considering the anti-inflammatory/anti-oxidative properties of both enzymes. A total of 63 sport and leisure horses’ sera were chosen among those routinely serologically examined on leptospirosis during the year 2009 in Croatia. Sera were divided into three groups according to the estimated level of antibody titre against Leptospira spp; group 1: sera serologically negative to leptospirosis (antibody titre<50) (n=21); group 2: sera with residual or anamnestic antibody titre (50–200) (n=23); group 3: sera with high antibody titre (≥1600) indicating recent Leptospira infection (n=19). Serum PAF-AH and PON1 activity was not significantly different between investigated groups (p>0.05). There were no statistical differences in lipid status parameters (p>0.05) among study groups as well. However, significant positive correlations (p<0.05) of PAF-AH and PON1 with total cholesterol and HDL–C were found. Results may indicate low levels of systemic inflammatory response and oxidative stress in horses with subclinical leptospirosis. Further studies with clinically manifested disease are needed to elucidate the potential role of PAF-AH and PON1 as prognostic markers of the leptospirosis outcome.

Serum platelet-activating factor acetylhydrolase activity: relationship with metabolic syndrome in women with history of gestational diabetes mellitus

Objective. The aim of this study was to evaluate plasma platelet-activating factor acetylhydrolase (PAF-AH) activity in euglycaemic women with history of gestational diabetes (GDM), and to explore whether this activity is associated with metabolic syndrome (MS) in this group of women.Methods. The cross-sectional study included 36 women with history of GDM and 40 women with history of normal glucose tolerance in pregnancy (control group).Results. Compared to the controls, the GDM group had significantly higher mean values for serum glucose, insulin, HOMA-IR, triglyceride, GGT and plasma PAF-AH activity, and a statistically higher prevalence of MS. Within the GDM group, women diagnosed with MS had significantly higher PAF-AH activity than those without MS (p = 0.002).Conclusion. This is the first study to have shown that plasma PAF-AH activity and GGT levels may be significant for evaluating atherosclerosis risk and metabolic hepatic damage in women with history of GDM.

Effect of Splenectomy and Autologous Spleen Transplantation on the Serum Platelet-Activating Factor Acetylhydrolase (PAF-AH) Activity and Acute Phase Response (APR) in a Porcine Model

The aim of this study was to evaluate the inflammatory response after total splenectomy and spleen autotransplantation in a porcine model by measuring serum platelet-activating factor acetylhydrolase activity, C-reactive protein and albumin concentrations. Nineteen piglets were used in the experiment. After induction of anesthesia, animals were randomly divided into three groups: sham-operation with spleens intact (n = 6), total splenectomy (n = 6), and splenic autotransplantation (n = 7) with small fragments of the spleen autotransplanted into the greater omentum. The blood samples were taken just before surgery and on day 1st, 5th, 12th, 26th and 40th postoperatively. PAF-AH activity, CRP and albumin concentrations were assayed in the sera. After total splenectomy, PAF-AH activity was significantly increased on day 5th, while there was no significant increase after spleen autotransplantation or the sham-operation. CRP was significantly increased after surgery in all experimental groups. Albumin was significantly decreased after surgery from day 5th until day 40th in splenectomized and autotransplanted pigs. Increased PAF-AH activity after splenectomy and spleen autotransplantation might be attributed to inflammatory conditions due to the loss of splenic tissue and trauma. Time-course increase of CRP, in all groups after surgery suggests post-injury inflammatory response due to tissue lesion during operation.

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.

Serum platelet-activating factor acetylhydrolase activity: A novel potential inflammatory marker in type 1 diabetes

Plasma activity of the platelet-activating factor acetylhydrolase (PAF-AH) plays an important role in inflammation and atherosclerotic process in chronic diseases. We aimed to evaluate the levels of PAF-AH activity and their association with the metabolic profile and chronic complications in patients with type 1 diabetes. The study included 118 outpatients (54 males) aged 27.1 ± 11.3 years with disease duration of 12.3 ± 8.5 years with ( n = 38) or without ( n = 80) diabetes complications and 96 control subjects (48 males) matched for age, gender, body mass index and smoking habits. The serum levels of PAF-AH activity were higher in patients either with or without chronic complications (16 ± 5.3 and 14 ± 5.4 nmol/(min mL), respectively) than in controls (13 ± 5.1 nmol/(min mL), P = 0.02). In the total population, PAF-AH activity was correlated with age, HDL-cholesterol, total cholesterol and LDL-cholesterol. In patients, PAF-AH activity was correlated with age, HbA1c, uric acid, HDL-cholesterol, cholesterol, LDL-cholesterol, cholesterol/HDL-cholesterol ratio and the LDL-cholesterol/HDL-cholesterol ratio. It is concluded that PAF-AH plasma activity could be a novel candidate for low-grade inflammatory marker in patients with type 1 diabetes.

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.

Diagnostic Value of the Serum Platelet-Activating Factor Acetylhydrolase Activity in Inflammatory Bowel Disease

Platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme hydrolyzing platelet-activating factor (PAF), a potent inflammatory mediator, but the relationship between this enzyme and inflammatory bowel disease (IBD) is not fully elucidated. The aim of the present study was to examine the usefulness of the serum PAF-AH activity in order to differentiate ulcerative colitis (UC) from Crohn's disease (CD). The serum PAF-AH activity was measured in 57 patients with IBD (39 UC and 18 CD patients) and 13 control subjects by a spectrophotometric method. The serum PAF-AH activity was thus found to be significantly lower in patients with CD (median 265.5 U/l) than in those with UC (355 U/l) or control subjects (374 U/l). This marker at a cutoff level of 386 U/l demonstrated a sensitivity of 46%, a specificity of 100%, and a positive predictive value of 100% regarding its ability to distinguish UC from CD. Moreover, the marker responded inversely to the changes in the disease activity of IBD. These results suggest that measuring the serum PAF-AH activity is a useful diagnostic modality for making a differential diagnosis between UC and CD.

Serum platelet-activating factor acetylhydrolase (PAF-AH) activity in patients with hyperbilirubinemic hepatobiliary disease

Platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme that catalyzes hydrolysis of PAF and is important for regulation of serum PAF concentration. Twenty-seven patients with hyperbililubinemic hepatobiliary diseases (eight patients with liver cirrhosis, five with acute hepatitis and 14 with obstructive cholestasis) were studied. Serum PAF-AH activity was elevated in hyperbilirubinemic condition associated with liver cirrhosis, obstructive cholestasis or acute hepatitis. There was a significant correlation of serum PAF-AH activity with serum cholesterol ( r=0.891, P=0.014 in liver cirrhosis, r=0.813, P=0.002 in obstructive cholestasis) or low density lipoprotein (LDL) cholesterol ( r=0.771, P=0.007 in obstructive cholestasis). Serum PAF-AH activity/cholesterol ratio and PAF-AH activity/LDL cholesterol ratio were elevated in the three types of hyperbilirubinemic liver disease. LDL cholesterol increased and PAF-AH/LDL cholesterol ratio decreased in acute hepatitis after remission. On the other hand, LDL cholesterol decreased and PAF-AH/LDL cholesterol ratio did not change after treatment in obstructive cholestasis. These findings suggest that, though serum LDL is a factor influencing serum PAF-AH activity in obstructive jaundice, other factors, i.e. reduced biliary PAF-AH excretion, may also influence serum PAF-AH activity in hyperbilirubinemic hepatobiliary diseases.

Serum platelet-activating factor acetylhydrolase (PAF-AH) activity in more than 3000 healthy Japanese

Background: A spectrophotometric assay for platelet-activating factor acetylhydrolase (PAF-AH) activity differs from the radioisotopic assay in its value because of a difference in substrate specificity. The spectrophotometric assay is more precise than the radioisotopic assay, providing information that is not clear with the radioisotopic assay. Methods: We measured the serum PAF-AH activity in 3106 healthy Japanese, utilizing the spectrophotometric assay with an Hitachi 7170 automatic analyzer. We also measured the serum PAF-AH activity in 18 healthy volunteers to investigate the effect of diet and the change in activity in a day and over 6 weeks. Changes were examined at 0 (day 1), 1, 2, 4 and 6 weeks. Results: The mean value for females was significantly lower than that of males at the 5% level and both male and female activity had a tendency to increase with advancing age. It is known that the PAF-AH is primarily associated with LDL in blood and the PAF-AH activity correlated with the total cholesterol ( r=0.52, n=126) and the LDL cholesterol ( r=0.60, n=126) concentrations. In the diet study, there was no observable effect on activity. No difference in PAF-AH activity was observed between serum and plasma sample types. The serum PAF-AH activity was stable at 7 °C for at least 7 days and at −20 °C for at least 2 months. Conclusions: The serum PAF-AH activity in women was lower than in men until the menopausal age was reached. We could use not only fresh fasting serum, but also plasma sample, non-fasting sample and stored sample to estimate the PAF-AH activity.

Increased activity of platelet-activating factor acetylhydrolase in low-density lipoprotein subfractions induces enhanced lysophosphatidylcholine production during oxidation in patients with heterozygous familial hypercholesterolaemia.

Patients with heterozygous familial hypercholesterolaemia (FH) have elevated plasma concentrations of low-density lipoprotein (LDL) and develop premature atherosclerosis. There is increasing evidence that oxidative modification of LDL is important for the pathogenesis of atherosclerosis, and the LDL-associated platelet-activating factor acetylhydrolase (PAF-AH) seems to play a key role in LDL oxidation by hydrolysing the oxidized phospholipids of phosphatidylcholine (PC) and producing lysophosphatidylcholine (lyso-PC). We measured the total serum and high-density lipoprotein (HDL) levels of PAF-AH activity and studied the distribution of PAF-AH activity among three LDL subfractions isolated by gradient ultracentrifugation in 15 patients with heterozygous FH and 13 normolipidaemic control subjects. We also determined the lyso-PC production in each LDL subfraction during Cu2(+)-induced oxidation in vitro. The total serum PAF-AH activity in heterozygous FH patients was significantly higher than in control subjects, whereas the HDL-associated PAF-AH activity, expressed as a percentage of total serum PAF-AH activity, was significantly lower in the FH patients than in control subjects (13.9 +/- 6.6% vs. 30.6 +/- 4.4%, P < 0.001). Among the LDL subfractions, the PAF-AH activity in both normolipidaemic control subjects and FH patients, expressed as nmol mg-1 protein min-1, was significantly higher in the LDL3 subfraction (33.1 +/- 4.8 and 53.4 +/- 11.5 respectively) than in the LDL2 (18.6 +/- 5.3 and 26.8 +/- 10.4 respectively, P < 0.0001 for both comparisons) and LDL1 subfractions (5.1 +/- 1.5 and 7.8 +/- 2.6, respectively, P < 0.0001 for both comparisons). Additionally, the enzyme activity in each LDL subfraction of the heterozygous FH patients was significantly higher than in control subjects (P < 0.02 for LDL1, P < 0.03 for LDL2 and P < 0.0001 for LDL3). No difference was observed in the susceptibility to oxidation of each LDL subfraction among the heterozygous FH patients and the normolipidaemic control subjects. During oxidation, the PAF-AH activity decreased, whereas the lyso-PC levels significantly increased in all subfractions of both groups. The lyso-PC/sphingomyelin molar ratio in each LDL subfraction of the FH patients 3 h after the onset of the oxidation was significantly higher than in control subjects [0.38 +/- 0.05 and 0.27 +/- 0.04, respectively, for LDL1 (P < 0.006), 0.47 +/- 0.08 and 0.39 +/- 0.03, respectively, for LDL2 (P < 0.04), 0.55 +/- 0.11 and 0.42 +/- 0.06, respectively, for LDL3 (P < 0.02)]. Our results show that heterozygous FH patients exhibit higher PAF-AH activity than control subjects in all LDL subfractions, resulting in higher lyso-PC production during oxidation, which confers on these subfractions higher biological potency. This phenomenon, in combination with the diminished anti-atherogenic and antioxidant capability of HDL in these patients due to the relatively low HDL-cholesterol levels compared with LDL-cholesterol levels and, consequently, the relatively low HDL-associated PAF-AH activity, could contribute to the higher atherogenicity and incidence of coronary artery disease observed in FH patients.

Serum Platelet-Activating Factor Acetylhydrolase Activity in Normal Pregnancy and Preeclampsia

Objective: The aim of this study was to elucidate the roles of platelet-activating factor acetylhydrolase (PAF-AH) in normal and hypertensive pregnancies.Method: Changes in serum PAF-AH activity were investigated in 13 nonpregnant women, 168 normal pregnant women, 11 women in normal puerperium, and 35 pregnant women with preeclampsia (mild: 28, severe: 7). Serum PAF-AH activity was measured by the method of Stafforini et al.Results: The serum PAF-AH activity of normal pregnant women between 5 and 34 weeks gestation was significantly lower than that of nonpregnant women, increasing after 34 weeks gestation and returning to nonpregnant levels within 1 month after delivery. In the pregnant women with mild preeclampsia at 28-41 weeks gestation, serum PAF-AH activity (28.0 ± 1.0 nmol/ min/mL, mean ± SEM, n = 28) was significantly (P < 0.01) higher than that in gestational-age-matched normal pregnant women (21.3 ± 0.8 nmol/min/mL, n = 73). However, in the pregnant women with severe preeclampsia, the activity (12.5 ± 3.9 nmol/min/mL, n = 7) was significantly lower (P < 0.01). Three of 7 severe preeclamptic patients showed extraordinarily low PAF-AH activity even before the onset of preeclampsia.Conclusion: We found remarkable differences between the serum PAF-AH levels in mild and severe preeclampsia. In mild preeclampsia, the increased PAF-AH activity may play a role in regulation of the local PAF concentration. On the other hand, some of the women with severe preeclampsia showed extraordinarily low PAF-AH activity, suggesting that such a regulatory mechanism of local PAF concentration may not operate in the patients.

Serum platelet-activating factor acetylhydrolase activity in rats with gastric ulcers induced by water-immersion stress.

Platelet-activating factor (PAF) acetylhydrolase is an enzyme which hydrolyzes PAF to yield inactive lysoPAF. This study focused on the influence of water-immersion stress on serum PAF acetylhydrolase activity. The enzyme activity was determined by measurement of [3H]acetate produced from 1-O-alkyl-2-[3H]acetyl-sn-glycero-3-phosphocholine upon precipitation of the complex of the radioactive substrate and albumin with trichloroacetic acid. The onset of water-immersion stress caused the development of gastric lesions associated with a significant increase in serum PAF acetylhydrolase activity. Serum PAF acetylhydrolase may leak into the blood from some tissues in rats with gastric injury induced by water-immersion stress and might control the action of PAF.

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

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 acetylhydrolase activity. The assay was based on measurement of [14C]acetate produced from 1-O-alkyl-2-[14C]-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 less than 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.

気管支ぜん息児童血清中のＰＡＦアセチルハイドロラーゼ活性

Platelet-activating factor (PAF) acetylhydrolase has been recognized as an enzyme to inactivate PAF. We developed the convenient method to determine human serum PAF acetylhydrolase activity, that was based on the measurement of [14C] -acetate from 1-O-alkyl-2- [14C] -acetyl-sn-glycero-3-phosphocholine on the precipitation of the complex of radioactive substrate and albumin by adding trichloro acetic acid to the incubation mixture. Thirty-two subjects with the deficiency of serum PAF acetylhydrolase were found in 816 healthy adult Japanese. The low PAF acetylhydrolase activity in the deficient serum was not due to the presence of the enzyme inhibitor. Both the sensitivity to PAF and the metabolism of PAF in platelets from subjects with PAF acetylhydrolase deficiency were almost the same as that of the normal subjects. The deficiency in serum PAF acetylhydrolase is apparently transmitted according to autosomal recessive heredity among four Japanese families.Asthmatic children were grouped into five classes (Remission, Wheezy, Mild, Moderate and Severe groups) on the basis of symptoms according to the grade of bronchial asthma of Japanese Society of Pediatric Allergy and Clinitical Immunology. The probability of PAF acetylhydrolase deficiency in group with severe symptoms (Moderate and Severe, 5 subjects per 42) was significantly higher than that in a healthy group without a history of wheezy (one subject per 36), a group with slight symptoms (Remission and Wheezy, one subject per 100) and healthy adult Japanese (32 subjects per 816) .These results suggest that the deficiency of serum PAF acetylhydrolase might be one of factors which lead asthmatic children to more severe state in respiratory symptoms.