Blood Platelet-activating Factor Research Articles

Elevated Platelet Activating Factor Level in Ischemia-Related Arrhythmia and Its Electrophysiological Effect on Myocardium

ObjectiveThe mechanism through which platelet activating factor (PAF) induces cardiac electrical activity and arrhythmia is not well understood and previous studies have suggested a potential involvement of ion channels in its action. The present study was aimed to clarify the role of PAF in fatal arrhythmias following acute myocardia infarction (AMI) and the underlying mechanism. Methods(1) Blood PAF levels were measured among 72 AMI patients at the time of diagnosis with AMI and 48 h later, and their electrocardiogram (ECG) was recorded continuously. (2) Ischemia simulation and surface electrocardiogram were conducted in 20 pigs and their PAF levels were measured. (3) PAF perfusion and standard microelectrode recording were performed on guinea pig papillary muscles. ResultsIn both humans and pigs, elevated PAF levels were detected in AMI and simulated ischemia, respectively, and even higher PAF levels were found when fatal arrhythmias occurred. In guinea pig myocardium, PAF induced a shortening of action potential duration at 90% level of repolarization (APD90)under non-ischemic conditions and a more pronounced shortening under early simulated ischemic conditions. ConclusionAMI and ischemia are associated with increased PAF levels in humans and pigs, which are further raised when fatal arrhythmia follows. The effects of PAF on the myocardium may be mediated by multiple ion channels.

In vivo antiatherogenic properties of olive oil and its constituent lipid classes in hyperlipidemic rabbits

Background and aim The consumption of olive oil has been associated with lower incidence of cardiovascular disease in the Mediterranean countries. This may be due in part to the action of platelet-activating factor (PAF) antagonists which we have previously demonstrated to be present in olive oil. In order to assess the in vivo effects of olive oil lipids and PAF in the development of atherosclerosis, the effects of diet supplementation with olive oil (OO), olive oil polar lipid extract (OOPLE) and olive oil neutral lipid extract (OONLE) were studied in rabbits fed a cholesterol-enriched diet. Methods and results Rabbits were fed for 45 days with atherogenic diet (Group A) supplemented with OO (Group B), OOPLE (Group C) or OONLE (Group D). Lipoprotein profiles, plasma in vitro oxidation, blood PAF levels, PAF-induced platelet aggregation and PAF-acetylhydrolase (PAF-AH) activity, were measured on day 0 and 45. Atherosclerotic lesions formed in the aortic wall and wall elasticity were assessed on day 45. Changes in lipid profile were in accordance with previous studies. Blood PAF levels were higher in group A and decreased in group D on day 45. In rabbits fed an atherogenic diet (Group A) blood PAF and PAF-AH increased, atherosclerotic lesions formed and the elasticity of vessel walls declined. In animals fed olive oil (Group B) or OOPLE (Group C) blood PAF-AH increased, platelet aggregation was attenuated, less oxidation occurred in plasma, lesion thickness was reduced and vessel walls retained elasticity. Most of these beneficial changes were not seen in animals fed OONLE (Group D) although blood PAF and plasma oxidation were lower. Conclusions The antiatherogenic effects of OO result from OOPLE. The beneficial effect of these factors is linked to PAF metabolism and proaggregant activity.

Platelet-activating factor (PAF) involvement in acetaminophen-induced liver toxicity and regeneration

Acetaminophen-induced toxicity has been attributed to cytochrome P-450-generated metabolites, which covalently modify target proteins. However, the mechanism of liver injury pathogenesis needs to be further elucidated. Platelet-activating factor (PAF) is one of the mediators involved in inflammatory tissue alterations associated with acute liver failure. In this study, alterations in blood PAF levels and the serum activity of PAF-acetylhydrolase (PAF-AH) were investigated over the time course of liver injury and regeneration induced by acetaminophen treatment in rats. The administration of a toxic dose of acetaminophen (3.5 g/kg) in rats caused acute hepatic injury, as evident by alterations of biochemical (serum enzymes: ALT, AST and ALP) and liver histopathological (degree of inflammation and apoptosis) indices between 20 and 40 h post-treatment. The hepatic damage was followed by liver regeneration, made evident by three independent indices ([3H]thymidine incorporation into hepatic DNA, liver thymidine kinase activity and hepatocyte mitotic index), presenting a peak at 72 h. The PAF levels were elevated at 24 and 28 h, presenting a remarkable peak at 32 h post-treatment. PAF-AH activity presented different kinetics to that of PAF. The enzyme activity was relatively low at all time points examined before the rise in PAF activity, peaking later, at 72, 84 and 96 h. Our data demonstrate that PAF is involved in the pathogenesis of acute liver failure and in augmented compensatory liver tissue repair post-acetaminophen treatment. However, the putative role of PAF during liver toxicity and regeneration remains to be established.

No evidence for a putative involvement of platelet-activating factor in systemic lupus erythematosus without active nephritis.

BACKGROUND: Platelet-activating factor (PAF) seems to be implicated in systemic lupus erythematosus (SLE) patients with associated renal diseases. AIMS: In this study, we ensured the role of PAF in SLE patients without renal complications. METHODS: Blood PAF and acetylhydrolase activity, plasma soluble phospholipase A(2), and the presence of antibodies against PAF were investigated in 17 SLE patients without active nephritis and in 17 healthy controls. RESULTS: Blood PAF levels were not different (p=0.45) between SLE patients (6.7+/-2.8 pg/ml) and healthy subjects (9.6+/-3.1 pg/ml). Plasma acetylhydrolase activity (the PAF-degrading enzyme) was significantly (p=0.03) elevated in SLE patients (57.8+/-6.4 nmol/min/ml) as compared with controls (37.9+/-2.6 nmol/min/ml). Plasma soluble phospholipase A(2) (the key enzyme for PAF formation) was not different (p=0.6) between SLE patients (59.1+/-5.1 U/ml) and controls (54.7+/-2.4 U/ml). Antibodies against PAF were detected only in 3/17 SLE patients. Flow cytometry analysis did not highlight PAF receptors on circulating leukocytes of SLE patients. CONCLUSION: This clinical study highlights no evidence for a putative important role of PAF in SLE patients without active nephritis.

Platelet-activating factor does not mediate circulatory failure induced by 35-GHz microwave heating.

Sustained whole-body exposure of anesthetized rats to 35-GHz radiofrequency radiation produces localized hyperthermia and hypotension, leading to circulatory failure and death. The physiological mechanism underlying the induction of circulatory failure by 35-GHz microwave (MW) heating is currently unknown. The purpose of this study was to determine whether platelet-activating factor (PAF) contributes to the hypotensive state induced by MW heating. Ketamine-anesthetized rats were instrumented for the measurement of arterial blood pressure, ECG and temperature at five sites. Administration of the PAF-receptor antagonist WEB 2086 (0.5 or 5 mg/kg) following the induction of circulatory failure (defined as a decrease in mean arterial blood pressure to 75 mmHg) failed to reverse the hypotension induced by MW heating and consequently did not alter the subsequent survival time. Furthermore, pretreatment with WEB 2086 at either dose did not alter subsequent mean arterial blood pressure, temperature responses to MW heating or survival time. Finally, MW heating did not alter either blood PAF levels or serum or lung PAF acetylhydrolase levels. Taken together, these results demonstrate that PAF does not mediate the hypotension induced by 35-GHz MW heating.

Is there a role of platelet-activating factor in human lung cancer?

Platelet-activating factor (PAF) is a lipid mediator that stimulates the in vitro growth of various human tumour cell lines and that enhances the effect of vascular endothelial growth factor that plays a key role during angiogenesis of human cancer. In this study, we assessed the levels of PAF and of the acetylhydrolase activity (AHA, the PAF degrading enzyme) in patients with lung cancer. Results indicated no significant differences between blood PAF amounts of lung cancer patients (91±33 pg/ml, n=31) and a control group of patients with chronic obstructive pulmonary disease (COPD) induced by habitual smoking (117±28 pg/ml, n=10). Similarly, their serum AHA levels were not different (67.9±3.0 nmol/min/ml as compared to 68.3±5.2 nmol/min/ml for lung cancer patients and controls, respectively). In contrast, PAF amounts were markedly ( P=0.01, t-test for paired data) reduced in the lung tumour tissues (77±29 pg/g, n=10) as compared to the non-tumour tissues (208±67 pg/g, n=10). These low levels of PAF were not related to a lower amounts of the lyso-PAF precursor but to an elevated ( P=0.01, t-test for paired data) AHA in the tumour tissues (37.0±4.9 nmol/min/g, n=10) as compared to the non-tumour tissues (24.6±2.6 nmol/min/ml, n=10). Reverse transcriptase polymerase chain reaction experiments showed the presence of the PAF receptor (PAF-R) transcript 1 but not transcript 2 in blood mononuclear cells of lung cancer patients and COPD patients. Flow cytometry experiments did not highlight differences in the number and the distribution of PAF-R on their circulating leukocytes. In conclusion, this clinical study highlights no evidence for a potential important role of PAF during human lung cancer.

Deregulated platelet-activating factor levels and acetylhydrolase activity in patients with idiopathic IgA nephropathy.

Platelet-activating factor (PAF) is a phospholipid mediator with potent inflammatory activities. PAF stimulates IgA synthesis by B cells while IgA aggregates enhance PAF production by neutrophils and mesangial cells. These results led us to investigate blood PAF levels and plasma acetylhydrolase (AHA, the PAF catabolic enzyme) activity in patients with idiopathic IgA nephropathy (IgAN). PAF and AHA levels were investigated using the platelet aggregation assay and degradation of (3)H-labelled PAF, respectively. The genotype of AHA with regard to the G994-->T mutation in exon 9 was assessed by an allele-specific polymerase chain reaction. Blood PAF levels were significantly (P:=0.003, Mann-Whitney U:-test) elevated in IgAN patients (50.6+/-6.8 pg/ml, n=33) compared with healthy controls (18+/-5 pg/ml, n=18). In contrast, plasma AHA levels were significantly (P:=0.0001, Mann-Whitney U:-test) reduced in patients with IgAN (61+/-2 nmol/ml/min, n=51) compared with healthy controls (78+/-4 nmol/ml/min, n=53). G994-->T transversion in exon 9 of AHA was not found in any of the IgAN patients. Elevated circulating levels of PAF in IgAN patients might result from an insufficient AHA probably related to environmental factors rather than genetic ones. The mechanism and the precise role of the PAF/AHA deregulation in IgAN patients remain to be clarified.

Nafamostat mesilate modulates the release of platelet-activating factor during left ventricular assistance with hemofiltration in canine heart failure

The enhanced generation of various chemical mediators is regarded as one of the mechanisms by which severe heart failure progresses to multiple organ failure. Platelet-activating factor is a phospholipid mediator which plays an important role in inflammatory reactions and circulatory shock. We studied the changes in platelet-activating factor levels in a canine heart failure model treated with a left ventricular assist device and hemofiltration, and assessed the effect of a protease inhibitor, nafamostat mesilate. Twenty dogs underwent multiple coronary ligations, and at 2 hours after the ligations they were maintained on left ventricular assist device support with continuous hemofiltration. The animals were divided into two groups: a nafamostat group (n = 10) that received nafamostat mesilate (2 mg/kg/hr), and a control group (n = 10) that received vehicle only. The blood platelet-activating factor level, before coronary ligations, in the control and nafamostat groups was 2.3 +/- 0.4 and 2.0 +/- 0.7 ng/ml, respectively, and the coronary ligations had little effect on the platelet-activating factor. However, after the initiation of left ventricular assist device, the platelet-activating factor in the control group (5.6 +/- 2.2) was significantly higher (p < 0.05) than that in the nafamostat group (1.1 +/- 0.3). Nafamostat administration was also effective in controlling the increase in the blood lactate level. Hemofiltration did not change the platelet-activating factor. We concluded that platelet-activating factor may play a critical role in the development of severe heart failure with left ventricular assistance, and nafamostat administration is likely to be beneficial in such a critical condition by suppressing the platelet-activating factor level.

Effect of Human Natural Xenoantibody Depletion and Complement Inactivation on Early Pig Kidney Function

Preformed xenoreactive natural antibodies (XNA) and complement mediate hyperacute xenograft rejection (HXR) in pig-to-human discordant xenotransplantation. In a pig kidney-human blood xenoperfusion model, we investigated whether XNA depletion and/or human complement inactivation preserved early pig kidney function. Pig kidneys were perfused for 180 min with pig blood (AUTO group, n = 8), human blood (HETER group, n = 6), complement-inactivated human blood (COMi group, n = 5), XNA-depleted human blood (ABd group, n = 5) or complement-inactivated and XNA-depleted human blood (ABd&COMi group, n = 5). HETER kidneys were rejected after 15–30 min and showed vascular microthrombi and interstitial hemorrhages. XNA depletion and/or complement inactivation prevented HXR. The glomerular filtration rate in ABd, COMi and ABd&COMi groups was significantly lower than in the AUTO group. Also, beyond 60 min, the COMi group showed a significantly lower glomerular filtration rate than that observed in ABd and ABd&COMi groups. Kidneys from ABd, COMi and ABd&COMi groups displayed endothelial cell edema, as well as higher soluble P-selectin levels and a higher renal myeloperoxidase content than the AUTO group kidneys. COMi and ABd&COMi groups had a significantly lower renal myeloperoxidase level than the HETER group. Also, in contrast to HETER and ABd groups, these complement-inactivated groups failed to show a positive correlation between P-selectin and renal myeloperoxidase. We also investigated platelet-activating factor (PAF) as possible mediator for these functional and pathologic changes. We found that blood PAF levels were similar in HETER, ABd, COMi and ABd&COMi groups and significantly higher than in the AUTO group. Also, when PAF was added to porcine endothelial cell monolayers, morphological changes due to cytoskeleton contraction were observed, and these changes were prevented by preincubation with a PAF receptor antagonist. In conclusion, although depletion of XNA and/or complement inactivation prevent HXR, the pig kidney function is not preserved at the level of the autologous combination. The PAF overproduction observed in the xenogenic combination, which is independent of the presence of XNA and complement, may be, at least in part, responsible for early endothelial cell morphological changes still present when HXR is prevented.

Eicosanoid and cytokine levels in plasma of patients during mesenteric infarction

Multible organ failure (MOF) induced by mesenteric infarction is associated with a high mortality rate. This study reports eicosanoid and cytokine levels in the blood of three atherosclerotic patients who ultimately died from MOF induced by mesenteric infarction. High plasma levels of 6- keto-prostaglandin (PG) F1α (the stable metabolite of PGI2), interleukin (IL)-6 and IL-8 are observed whereas plasma tumour necrosis factor alpha (TNFα), TxB2 (the stable metabolite of TxA2), PGE2, leukotrienes (LT)B4 and LTC4, and whole blood platelet-activating factor levels are not different from values obtained in similarly severe atherosclerotic patients. This short report questioned the clinical involvement of TNFα during such a pathology where a persistent translocation of endotoxin has been observed through the gut endothelial barrier. Activation of phospholipase A2 is suggested by the increase in the stable metabolite of PGI2 and might be by itself or through lipidic metabolites, a major systemic stimulus of IL-6 and IL-8 production.

Altered platelet-activating factor levels and acetylhydrolase activities are associated with increasing severity of bronchopulmonary dysplasia.

Lipid inflammatory mediators are thought to play an important role in the pathogenesis of neonatal lung injury and bronchopulmonary dysplasia (BPD). Because preliminary studies from the intensive care nursery of the University of Tennessee Medical Center, Knoxville, revealed linear increased in blood platelet-activating factor (PAF) levels in very low birthweight infants developing chronic lung disease and lower cord blood PAF acetylhydrolase activities in premature infants, it was theorized that altered platelet-activating factor levels and PAF acetylhydrolase activities are associated with increasing severity of BPD. Platelet-activating factor levels (blood and tracheal lavage) and PAF acetylhydrolase activities (blood and tracheal lavage) were measured over days 1 to 2, 3 to 5 and 6 to 7 in 16 ventilated infants and weekly in 9 infants with bronchopulmonary dysplasia. Platelet-activating factor values were normalized per nanogram of lavage blood urea nitrogen. Severity of bronchopulmonary dysplasia was estimated using the scoring system developed by Toce. Mean blood and lavage PAF levels and PAF acetylhydrolase activities were compared in infants developing bronchopulmonary dysplasia with those without the disease over the first seven days of life. Infants developing chronic lung disease were significantly smaller and of younger gestational age. In infants with bronchopulmonary dysplasia, higher PAF levels in blood were seen on days 3 to 5, along with increased lavage acetylhydrolase activities on days 1 to 2. Increased levels of PAF in lavage on days 3 to 5 were associated with increasing severity of bronchopulmonary dysplasia. Altered blood and lavage platelet-activating factor levels and PAF acetylhydrolase activities appear to be associated with the pathogenesis and severity of bronchopulmonary dysplasia.

Altered Platelet-Activating Factor Levels and Acetylhydrolase Activities Are Associated With Increasing Severity of Bronchopulmonary Dysplasia

<h2>ABSTRACT:</h2> Lipid inflammatory mediators are thought to play an important role in the pathogenesis of neonatal lung injury and bronchopulmonary dysplasia (BPD). Because preliminary studies from the intensive care nursery of the University of Tennessee Medical Center, Knoxville, revealed linear increases in blood platelet-activating factor (PAF) levels in very low birth-weight infants developing chronic lung disease and lower cord blood PAF acetylhydrolase activities in premature infants, it was theorized that altered platelet-activating factor levels and PAF acetylhydrolase activities are associated with increasing severity of BPD. Platelet-activating factor levels (blood and tracheal lavage) and PAF acetylhydrolase activities (blood and tracheal lavage) were measured over days 1 to 2, 3 to 5 and 6 to 7 in 16 ventilated infants and weekly in 9 infants with bronchopulmonary dysplasia. Platelet-activating factor values were normalized per nanogram of lavage blood urea nitrogen. Severity of bronchopulmonary dysplasia was estimated using the scoring system developed by Toce. Mean blood and lavage PAF levels and PAF acetylhydrolase activities were compared in infants developing bronchopulmonary dysplasia with those without the disease over the first seven days of life. Infants developing chronic lung disease were significantly smaller and of younger gestational age. In infants with bronchopulmonary dysplasia, higher PAF levels in blood were seen on days 3 to 5, along with increased lavage acetylhydrolase activities on days 1 to 2. Increased levels of PAF in lavage on days 3 to 5 were associated with increasing severity of bronchopulmonary dysplasia. Altered blood and lavage platelet-activating factor levels and PAF acetylhydrolase activities appear to be associated with the pathogenesis and severity of bronchopulmonary dysplasia.

PAF and haematopoiesis XII: macrophage colony-stimulating factor (M-CSF) decreases platelet-activating factor (PAF) acetylhydrolase production in macrophagic J774 cells.

Platelet-activating factor (PAF) is a phospholipid mediator with major immunoregulatory activities. Macrophages produce PAF acetylhydrolase activity, which regulates blood PAF concentrations. Macrophage colony-stimulating factor (M-CSF) is involved in the differentiation and functions of cells from the monocytic/macrophagic lineage. We found that murine macrophagic J774 cells metabolized PAF with lyso PAF as the major metabolite product. As in mouse plasma, the metabolism of PAF by J774 cells was not inhibited by PMSF, p-BPB, DTNB and quinacrine, M-CSF (100-5000 U/ml) significantly decreased PAF acetylhydrolase activity of the J774 cell without exhibiting a significant effect on cell growth. Elevated concentrations of M-CSF are found in blood and tissues during inflammatory states. It could be suggested that a decreased PAF catabolism by tissue macrophages in response to M-CSF may induce local elevated PAF concentrations, thus amplifying the inflammatory response.

Biochemical and cellular effects of heparin-protamine injection in rabbits are partially inhibited by a PAF-acether receptor antagonist

The origin of the thrombocytopenia and leucopenia induced by protamine-heparin complexes is unknown. We studied the biochemical and cellular effects of protamine (6 mg × kg −1, i.v.) injected after heparin (5 mg × kg −1, i.v.) in New Zealand rabbits. After protamine injection (0.5 min) increases in blood platelet-activating factor (PAF-acether, PAF) (27.6 ± 27.6 to 148.2 ± 48.9 pg × ml −1, P < 0.05), thrombocytopenia (403 ± 64 to 166 ± 13 cells × 10 −3 × mm −3, P < 0.05) and leucopenia (7650 ± 930 to 4300 ± 668 cells × mm −3, P < 0.05) were noted. Plasma thromboxane B 2 increased at 1 min (125.6 ± 24.4 to 879.7 ± 141.0 pg × ml −1, P < 0.01). Protamine alone induced no change. Indomethacin (3 mg × kg −1, i.v.) did not counteract the effects of heparin-protamine. Pretreatment with the PAF receptor antagonist BN 52021 [9 H1,7a-(epoxymethano)-1 H,6a H-cyclopenta[c]furo[2,3-b]furo-[3′,2′,3,4]cyclopenta[1,2- d]furan-5,9,12-(4 H)trione,3-tert-butylhexa hydroxy-8 methyl] alone (3 mg × kg −1, i.v.) delayed thrombocytopenia and reduced plasma thromboxane B 2 concentration but did not modify leucopenia. Thus thrombocytopenia and thromboxane B 2 release triggered by heparin-protamine may be potentiated by the release of PAF.

A clinical study on the significance of platelet-activating factor in the pathophysiology of septic disseminated intravascular coagulation in surgery

To investigate the characteristic differences between disseminated intravascular coagulation (DIC) found in surgical sepsis (septic DIC) and those found in patients with advanced gastrointestinal cancer (cancer DIC), we focused on two substances, endotoxin and platelet- activating factor (PAF). Coagulation test values were determined in 36 patients with DIC, and endotoxin and PAF concentrations in 13 of these patients. Seven septic patients were given a PAF antagonist to evaluate its usefulness in treating thrombocytopenia. Blood PAF and endotoxin concentrations were higher in patients with septic DIC, but they were almost normal in those with cancer DIC. Blood PAF concentrations showed a strong positive relationship to endotoxin only in septic DIC. There was a negative correlation between PAF concentrations and platelet counts in septic patients; platelet counts gradually increased after the administration of a PAF antagonist. PAF is inversely associated with platelet counts in patients with septic DIC. A PAF antagonist showed marked inhibitory effects on the characteristic changes of septic DIC, especially thrombocytopenia.

Platelet aggregability to platelet activating factor at rest and after exercise in patients with coronary artery disease.

The platelet response to the aggregatory effect of platelet-activating factor (PAF) in relation to blood PAF levels, serum PAF-acetylhydrolase (PAF-AH) activity and to their lipidaemic profile, was studied in 44 patients with coronary artery disease undergoing exercise tests. The PAF EC50 values in 21 patients with positive exercise test results were found to be significantly decreased at rest compared with 21 normal subjects (12.6 +/- 3.9 nM and 24.9 +/- 11.7 nM respectively) (P<0.0001). Moreover, the maximal percentage of aggregation to 50 nM PAF was found to be significantly increased (20.0 +/- 4.3% vs 13.5 +/- 3.6%, respectively) (P<0.0001). By contrast, the PAF EC50 values and the maximal percentage of aggregation in 23 patients with negative exercise test results were not statistically significantly different from the control group (25.2 +/- 11.4 nM and 14.1 +/- 4.7%, respectively). At the end of exercise, the PAF EC50 values and the maximal percentage of aggregation did not change in any group, and there were no significant differences in the whole-blood PAF levels either at rest or at the end of exercise. In patients with positive exercise test results, the PAF-AH activity at rest was significantly higher compared with the control group (37.2 +/- 8.0 nmol.ml(-1).min(-1) vs 32.4 nmol.ml(-1).min(-1), (P<0.03), whereas the enzyme activity did not differ in patients with negative exercise test results compared to controls (33.6 +/- 6.1 nmol.ml(-1).min(-1)). There was no change in PAF-AH activity during exercise in any group. The enzyme activity was positively correlated to the serum total and low density lipoprotein (LDL) cholesterol levels in the control group and in patients with negative exercise test results, whereas no correlation was found between PAF-AH activity and total or LDL cholesterol levels in patients with positive exercise test results.

PAF and hematopoiesis. II. Elevated levels of plasma paf acetylhydrolase after rapid infusion of 5-fluorouracil in cancer patients

Blood platelet-activating factor (PAF) levels are regulated by a plasma PAF acetylhydrolase. We investigated its levels in cancer patients during the course of a 5-day 5-fluorouracil (5-FU) treatment. PAF acetylhydrolase increased in nine patients with daily bolus infusion of 0.4 g 5-FU per m 2 of body surface (81.7 ± 8.7 nmol PAF/min/ml vs. 66.6 ± 7.0; P < 0.001 for day 5 as compared to day 1). By contrast PAF acetylhydrolase did not change in seven patients with continuous infusion of 5-FU. The meaning of these results is discussed in respect of the immunoregulatory role of PAF.

Increased levels of blood platelet‐activating factor in bronchial asthmatic patients with active symptoms

Levels of platelet-activating factor (PAF) in blood from 12 bronchial asthmatic patients (six atopic and six nonatopic) were measured by radioimmunoassay after lipid extraction and separation by high-performance liquid chromatography. None of the patients were given disodium cromoglycate and prednisolone, and they were instructed to take only regular medications during the tests. Blood was drawn from the patients in a fasting state, and PAF levels were compared between the times when they were free of asthmatic symptoms and when they had mild spontaneous attacks. Ten (six atopic and four nonatopic) out of 12 patients, when they had the asthmatic attacks, showed higher levels of PAF than when they were free of the symptoms. Blood PAF levels of the patients with the active symptoms were significantly higher than those of normal healthy control subjects, suggesting that PAF may play a role in bronchial asthma.

Metabolism of platelet-activating factor in neutrophils isolated from Pichinde virus-infected guinea pigs.

Metabolism of platelet-activating factor (PAF) was studied in cultured polymorphonuclear neutrophils (PMNs) obtained from Pichinde virus-infected strain 13 guinea pigs. Neutrophils obtained from control and infected guinea pigs on postinoculation days 10 and 14 were incubated with [3H]lyso-PAF, [3H]PAF, or [3H]acetate. After incubation for 1 h at 37 degrees C, formation of [3H]acyl-PAF from either [3H]lyso-PAF or [3H]PAF increased significantly in PMNs from infected guinea pigs compared to control PMNs. Furthermore, total radioactivity from [3H]lyso-PAF or [3H]PAF was higher in PMNs from infected animals than in those from controls. However, compared to PAF production by control PMNs, production of PAF by infected PMNs was unchanged. These results suggest that PMNs may not be the major source of increased blood PAF levels during Pichinde viral disease.

Increased levels of blood platelet-activating factor (PAF) and PAF-like lipids in patients with ischemic stroke.

Levels of platelet-activating factor (PAF) in blood from patients with ischemic stroke were determined by radioimmunoassay (RIA). Using 2 ml of blood as a starting material, PAF was detected in 11 out of 17 stroke patients and 3 of 25 age-matched healthy controls. This implies that blood level of PAF is higher in stroke patients than in controls. Plasma levels of PAF-like lipid(s) (PAF-LL) were also estimated in the same subjects by a bioassay based on aggregation of human polymorphonuclear neutrophils. PAF-LL was detected in plasma samples of all subjects and the average values in patients and controls were 294 +/- 211 pg/ml and 140 +/- 122 pg/ml, respectively. There was a statistically significant difference between these two values (p less than 0.01). Separation of plasma lipids by HPLC gave a single peak in bioassay, which had the same elution volume as authentic PAF. When each fraction was subjected to RIA, the fractions corresponded to phosphatidylcholine (PC) or lysoPC also showed the immunoreactivity, however, the purification procedure using an octadecylsilica gel cartridge eliminated such cross-reacting compounds. We conclude that blood PAF is higher in patients with ischemic stroke than in healthy subjects. Besides, there may be bioactive phospholipid molecules other than PAF, which level in plasma is also higher in stroke patients.