RESUMEN
The effects of platelet activating factor (PAF) and its cell analogs 1-O-alk-1;-enyl-2-acetyl-sn-glycero-3-phosphocholine (1-alkenyl-PAF) and 1-acyl-2-acetyl-sn-glycero-3-phosphocholine (1-acyl-PAF) on chemotaxis of human leukocytes in vitro and their inflammatory and antiinflammatory activities in vivo were studied. Both analogs stimulated chemotaxis of human leukocytes in agarose gel. PAF and 1-alkenyl-PAF induced rat paw edema in the range of doses 0.1-10 and 10-100 micro g per paw, respectively. Paw edema induced by 1-acyl-PAF (10-100 micro g per paw) was more pronounced than that induced by PAF or 1-alkenyl-PAF. The latter also exhibited significant antiinflammatory effect by inhibiting PAF- or carrageenan-induced rat paw edema, and this effect exceeded that of dexamethasone. In these models of inflammation 1-acyl-PAF did not exhibit any antiinflammatory activity. The data suggest that PAF is not the only cell phospholipid mediating inflammation--its cell analogs, 1-acyl-PAF and 1-alkenyl-PAF, may also be involved into the inflammatory response. Possible interrelationships between cellular synthesis of 1-acyl-PAF, its formation in oxidized LDL, biological effects of lysolecithin, and penetration of LDL into the arterial wall are discussed.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Quimiotaxis de Leucocito/efectos de los fármacos , Leucocitos/metabolismo , Factor de Activación Plaquetaria/análogos & derivados , Factor de Activación Plaquetaria/farmacología , Acilación , Animales , Carragenina/antagonistas & inhibidores , Carragenina/toxicidad , Bovinos , Modelos Animales de Enfermedad , Edema/inmunología , Edema/metabolismo , Edema/patología , Miembro Posterior/patología , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/patología , Leucocitos/citología , Leucocitos/inmunología , Plasmalógenos/química , Plasmalógenos/metabolismo , Factor de Activación Plaquetaria/antagonistas & inhibidores , Factor de Activación Plaquetaria/metabolismo , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
The influence of the phospholipid platelet-activating factor (PAF), its cell analogs, and lipid PAF antagonist on the production of superoxide radicals by leukocytes isolated from the blood of healthy and hypercholesterolemia IIA individuals was studied. It was found that endogenous superoxide production level in the leukocytes of hypercholesterolemic individuals more than 4-5 times higher than in the leukocytes of healthy individuals. Exogenous PAF stimulates the superoxide production in the leukocytes of healthy individuals but significantly inhibits the superoxide production in the leukocytes of hypercholesterolemic individuals. The compounds 1-acyl-2-acetyl-sn-glycero-3-phosphocholine (1-acyl-PAF) and 1-alk-1;-enyl-2-acetyl-sn-glycero-3-phosphocholine (1-alkenyl-PAF) only slightly inhibited the endogenous superoxide production in the leukocytes of hypercholesterolemia individuals. However, pretreatment of leukocytes by 1-alkenyl-PAF or PAF-antagonist (1-O-alk-1;-enyl-2-(2;-acetoxybenzoyl)-sn-glycero-3-phosphocholine) results in a 50% inhibition of the PAF-induced superoxide production by leukocytes of healthy individuals. This PAF-antagonist alone or in combination with PAF induces a substantial (65-70%) inhibition of superoxide production in the leukocytes of hypercholesterolemic individuals. It is concluded that superoxide production by leukocytes of healthy individuals and especially by leukocytes of hypercholesterolemic individuals is process that depends on PAF or PAF-like lipids.
Asunto(s)
Hipercolesterolemia/sangre , Leucocitos/metabolismo , Factor de Activación Plaquetaria/metabolismo , Superóxidos/metabolismo , Animales , Bovinos , Humanos , Técnicas In Vitro , Factor de Activación Plaquetaria/análogos & derivados , Factor de Activación Plaquetaria/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The influence of acetyl salicylic acid (ASA) derivatives with platelet-activating factor (PAF) lipid analogs on PAF-induced human platelet aggregation has been studied. It was found that the ASA amide with an ethanolamine plasmalogen PAF analog (1-0-alk-1'-enyl-2-acetyl-sn-glycero-3-phospho-(N-2'-acetoxybenzoyl)ethanolamine) and the ASA ester with a choline plasmalogen PAF analog (1-0-alk-1'-enyl-2-(2'-acetoxybenzoyl)-sn-glycero-3-phosphocholine) at concentrations of 10-7-10-6 M effectively inhibit PAF-induced aggregation of human platelets. In contrast to these compounds, the ASA amide with an alkyl PAF analog (1-0-alkyl-2-acetyl-sn-glycero-3-phospho-(N-2'-acetoxybenzoyl)ethanolamine) did not inhibit PAF-induced platelet aggregation. As possible mechanisms of action of the studied compounds, the blockade of PAF-receptor and cyclooxygenase inhibition are proposed.
Asunto(s)
Factor de Activación Plaquetaria/análogos & derivados , Factor de Activación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Ácido Salicílico/farmacología , Amidas/química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Ésteres/química , Humanos , Estructura Molecular , Ácido Salicílico/químicaRESUMEN
The influence of an amide of prostaglandin E1 and ethanolamine plasmalogen platelet-activating factor analog 1-O-alk-1;-enyl-2-acetyl-sn-glycero-3-phospho-(N-11alpha, 15alpha-dioxy-9-keto-13-prostenoyl)ethanolamine (PGE1-PPAF) on platelet-activating factor (PAF)-, ADP-, and thrombin-induced human platelet aggregation has been studied. It was found that PGE1-PPAF inhibits the PAF-, ADP-, and thrombin-induced platelet aggregation in platelet-rich plasma. 1-O-alk-1;-enyl-2-acetyl-sn-glycero-3-phosphoethanolamine inhibited PAF-induced aggregation up to 50% but had no influence on platelet aggregation induced by ADP or thrombin. The ethanolamine plasmalogen analog of PAF 1-O-alk-1;-enyl-2-acetyl-sn-glycero-3-phospho-(N-palmitoyl)ethanolami ne, having a palmitoyl residue instead of PGE1, did not inhibit platelet aggregation induced by PAF, ADP, or thrombin. We propose that inhibition of human platelet aggregation by PGE1-PPAF is mediated by its action on platelet PAF-receptors and the adenylate cyclase system.
Asunto(s)
Amidas/metabolismo , Fosfatidiletanolaminas/farmacología , Plasmalógenos/metabolismo , Factor de Activación Plaquetaria/análogos & derivados , Factor de Activación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Alprostadil/química , Alprostadil/metabolismo , Plaquetas/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Fosfatidiletanolaminas/química , Plasmalógenos/química , Factor de Activación Plaquetaria/química , Trombina/farmacologíaRESUMEN
The interaction of a plasmalogenic analog of platelet-activating factor (1-O-alk-1;-enyl-2-acetyl-sn-glycero-3-phosphocholine; 1-alkenyl-PAF) with human platelets was studied. 1-Alkenyl-PAF induced an increase in intracellular Ca2+ concentration and inhibition of adenylate cyclase at significantly higher concentrations than PAF. 1-Alkenyl-PAF inhibits PAF-induced platelet aggregation but has no effect on ADP- or thrombin-induced aggregation of human platelets. In contrast to PAF, 1-alkenyl-PAF increases [3H]PGE1 binding with human platelets. The properties of 1-alkenyl-PAF as an agonist or antagonist of PAF receptors apparently depend on its concentration in the cell medium. Under physiological conditions 1-alkenyl-PAF might be a natural PAF antagonist acting in the human cardiovascular system.
Asunto(s)
Plaquetas/fisiología , Plasmalógenos/fisiología , Factor de Activación Plaquetaria/fisiología , Inhibidores de Adenilato Ciclasa , Alprostadil/metabolismo , Azepinas/farmacología , Calcio/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Cinética , Triazoles/farmacologíaRESUMEN
The level of lipoprotein oxidation in blood sera of pregnant women with obstetrical abnormalities is studied. Lipid peroxides were measured by a modified thiobarbituric acid test. The level of lipoprotein oxidation was increased, which may be one of the pathogenetic mechanisms of vascular disease in fetoplacental insufficiency and gestosis.
Asunto(s)
Lipoproteínas/sangre , Complicaciones del Embarazo/metabolismo , Adulto , Femenino , Humanos , Peróxidos Lipídicos/sangre , Malondialdehído/sangre , Oxidación-Reducción , Insuficiencia Placentaria/sangre , Insuficiencia Placentaria/metabolismo , Preeclampsia/sangre , Preeclampsia/metabolismo , Embarazo , Complicaciones del Embarazo/sangreRESUMEN
The role of platelet-activating factor (PAF, a phospholipid compound) in regulation of cell functions and cell-cell interactions is reviewed. The biological effects of PAF on platelets, neutrophils, basophils, eosinophiles, lymphocytes, and endothelial cells are described. Mechanisms of cell activation by PAF are discussed. Interactions of PAF with other biological regulators (prostaglandins, leukotrienes, NO, tumor necrosis factor, and interleukins) are considered.
Asunto(s)
Factor de Activación Plaquetaria/fisiología , Receptores de Superficie Celular , Receptores Acoplados a Proteínas G , Animales , Comunicación Celular/fisiología , Interacciones Farmacológicas , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiología , Humanos , Técnicas In Vitro , Leucocitos/efectos de los fármacos , Leucocitos/fisiología , Factor de Activación Plaquetaria/análogos & derivados , Factor de Activación Plaquetaria/farmacología , Activación Plaquetaria/efectos de los fármacos , Activación Plaquetaria/fisiología , Glicoproteínas de Membrana Plaquetaria/fisiologíaAsunto(s)
Hiperlipoproteinemia Tipo II/sangre , Estrés Oxidativo , Adulto , Antioxidantes/metabolismo , Biomarcadores/sangre , Complemento C3a/análogos & derivados , Complemento C3a/metabolismo , Complemento C5a des-Arginina/metabolismo , Humanos , Mediadores de Inflamación/sangre , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Factor de Activación Plaquetaria/farmacología , Superóxidos/metabolismo , Vitamina E/sangreRESUMEN
A modified ELISA is proposed for detecting antiphospholipid antibodies of the IgM and IgG isotypes, including antibodies to cardiolipin, phosphatidylserine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylcholine, and sphingomyelin in human blood serum. The degree of phospholipid saturation, its phase (lamellar or hexagonal), purity, oxidation index of the phospholipid preparation, and conditions of solid phase treatment are important factors providing a sufficiently high sensitivity and reliability of measurements. The clinical value of the method was demonstrated in examinations of 70 patients with habitual abortions. The method can be used in studies of the spectrum of antiphospholipid antibodies in different diseases involving an increase of their blood serum level.
Asunto(s)
Anticuerpos Antifosfolípidos/análisis , Técnicas para Inmunoenzimas , Adulto , Anticuerpos Anticardiolipina/inmunología , Autoanticuerpos/análisis , Cromatografía en Capa Delgada , Femenino , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Fosfatidilcolinas/inmunología , Fosfatidiletanolaminas/inmunología , Fosfatidilinositoles/inmunología , Fosfatidilserinas/inmunología , Embarazo , Esfingomielinas/inmunologíaRESUMEN
This review considers the relation between the evolution of ether lipids and platelet-activating factor (PAF) in living organisms for the first time. Ether lipids are shown to be the main structural lipid components in the cells of the most primitive organisms on the Earth; during evolution they were gradually substituted for lipids with ester and vinyl bonds. Synthesis of PAF has been found in some bacteria, protozoans, yeasts, plants, marine invertebrates, lower vertebrates, and mammals. The regulatory role of PAF is suggested to already appear in protozoans and later be maintained during the subsequent evolution of living organisms. During evolution, functions of PAF in the cell have been changing and enlarging, while ether lipids have been gradually losing their role as the main structural lipid component of the cells of living organisms.
Asunto(s)
Éteres Fosfolípidos/metabolismo , Factor de Activación Plaquetaria/genética , Factor de Activación Plaquetaria/metabolismo , Animales , Bacterias/metabolismo , Evolución Molecular , Hongos/metabolismo , Invertebrados/metabolismo , Mamíferos/metabolismo , Vertebrados/metabolismoRESUMEN
The review is concerned with cell metabolites - the platelet activating factor (PAF) and its choline-containing structural analogs. The biological activity of PAF and its analogs are considered. The influence of PAF and its analogs of membrane properties, cell receptors, transmembrane signalling (protein kinase C activation, Ca2+ release) as well as its participation in cell phospholipases A2, C and D activation are considered. The intracellular function of PAF and its analogs is discussed in terms of their influence on prostaglandin and leukotriene biosynthesis as well as with reference to the biological activity of 1-acyl-2-acetyl-sn-glycerols and lysophosphatidylcholine. The function of cell-released PAF and its analogs is considered in connection with their influence on plasma lipoproteins, inter-cell PAF synthesis and different mechanisms of PAF and PAF analog-induced cell activation including cell priming, cell desensitization and receptor-dependent effects. It is concluded that PAF is an intracellular and intercellular mediator, whereas 1-acyl-PAF is an intracellular lipid bioregulator.
Asunto(s)
Factor de Activación Plaquetaria/metabolismo , Animales , Membrana Celular/metabolismo , Colina/análisis , Humanos , Factor de Activación Plaquetaria/biosíntesis , Factor de Activación Plaquetaria/química , Receptores de Superficie Celular/metabolismoRESUMEN
The influence of sn-2-acetylated analogs of phosphatidalic acid on the release reaction and aggregation of human platelets has been studied. It was found that phosphate-, phosphorylethanolamine- or phosphorylcholine-containing sn-2-acetylated analogs of phosphatidalic acid do not stimulate human platelet aggregation but inhibit the platelet-activating factor (PAF) induced platelet aggregation. The phosphatidalic acid analog, I-O-alk-1'-enyl-2-acetyl-sn-glycero-3-phosphate, stimulates human platelet release reaction measured by acridine orange release from human platelets in the same extent as does PAF. Other phosphatidalic acid analogs (1-O-alk-1'-enyl-2-acetyl-sn-glycero-3-phosphoethanolamine, 1-O-alk-1'-enyl-2-acetyl-sn-glycero-3-phosphocholine) inhibit acridine orange exocytosis from PAF-stimulated human platelets. It is concluded that the activity of sn-2-acetylated phosphatidalic acid analogs towards human platelets differs from those of corresponding ester and ether phosphatidalic acid analogs and, consequently, they may have another functional significance in the processes of platelet activation.
Asunto(s)
Ácidos Fosfatidicos/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Acetilación , Humanos , Ácidos Fosfatidicos/química , Factor de Activación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/químicaRESUMEN
A platelet-activating factor (PAF) antagonist was found to inhibit superoxide production in the leukocytes of patients with type IIA hypercholesterolemia. PAF (10(-7)-10(-6) M) alone failed to stimulate superoxide production in intact or PAF-antagonist-treated leukocytes. The PAF-antagonist-induced inhibition of superoxide production was observed in the leukocytes from hypercholesterolemic patients whose plasma cholesterol levels varied from 8.3 to 14.0 mmole/l.
Asunto(s)
Hipercolesterolemia/sangre , Leucocitos/efectos de los fármacos , Fosfatidilcolinas/farmacología , Factor de Activación Plaquetaria/antagonistas & inhibidores , Superóxidos/antagonistas & inhibidores , Humanos , Leucocitos/metabolismoRESUMEN
The effects of the platelet-activating factor (PAF) and the methoxy-PAF analog, 1-O-alkyl-2-methoxy-sn-glycero-3-phosphocholine, on platelet activation, oxidative burst in neutrophils and proliferation of K-562 and P815 cells have been studied. It has been found that the biological activity of methoxy-PAF for human platelets and neutrophils is commensurate with that of PAF. However, the cytotoxic properties of methoxy-PAF are much stronger than the cytotoxicity of PAF for tumour cells. It is concluded that the biological activity of methoxy-PAF is, to a great extent, due to its close structural resemblance to PAF as well as to the inability of cells to perform rapid metabolism of methoxy-PAF.
Asunto(s)
Neutrófilos/efectos de los fármacos , Fosfatidilcolinas/farmacología , Factor de Activación Plaquetaria/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Decapodiformes , Humanos , Ratones , Neutrófilos/metabolismo , Células Tumorales CultivadasRESUMEN
Recent data concerning two structural platelet-activating factor (PAF) analogs-1-O-acyl-2-acetyl-sn-glycero-3-phosphocholine (acyl-PAF) and 1-O-alk-1'-enyl-2-acetyl-sn-glycero-3-phosphocholine (vinyl-PAF) identified in some cells and tissues are reviewed. Isolation, identification, biosynthesis, and metabolism of acyl-PAF and vinyl-PAF are considered. The activity of acyl-PAF and vinyl-PAF towards platelets, leukocytes, isolated myocardium, and ileum as well as its in vivo activity are discussed. The influence of acyl-PAF and vinyl-PAF on PAF platelet interaction, Ca2+ mobilization, and platelet adenylate cyclase activity is considered. It is concluded that similar to PAF, acyl-PAF and vinyl-PAF should be regarded as a family of PAF lipid bioregulators.
Asunto(s)
Lípidos/fisiología , Fosfatidilcolinas/fisiología , Plasmalógenos/química , Factor de Activación Plaquetaria/análogos & derivados , Acilación , Técnicas In Vitro , Factor de Activación Plaquetaria/fisiologíaRESUMEN
The effects of plasmalogenic and acyl structural analogs of the platelet activation factor (PAF) on the superoxide radical production by human blood leukocytes were studied. It was found that 1-O-acyl-2-acetyl-sn-glycero-3-phosphocholine and 1-O-(1'-alkenyl)-2-acetyl-sn-glycero-3-phosphocholine stimulates the production of leukocyte superoxide radicals, their activity being comparable with that of PAF. Stimulation of superoxide radical production strongly depends on the structure of the polar heads of PAF analogs. It is supposed that choline-containing plasmalogenic and acyl PAF analogs may act as specific lipid mediators of the neutrophil function.
Asunto(s)
Leucocitos/metabolismo , Factor de Activación Plaquetaria/farmacología , Superóxidos/metabolismo , Acilación , Aldehídos/metabolismo , Radicales Libres , Humanos , Factor de Activación Plaquetaria/análogos & derivadosRESUMEN
The pro- and anti-inflammatory activity of new structural analogues of the platelet-activating factor (PAF) was studied. It was found that three PAF analogues inhibit PAF-induced rat paw edema in a dose-dependent manner. The anti-inflammatory activity of one of the PAF analogues upon PAF- or carrageenan-induced inflammation was comparable or in some extent exceeded that of dexamethasone.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Factor de Activación Plaquetaria/análogos & derivados , Factor de Activación Plaquetaria/uso terapéutico , Animales , Antiinflamatorios/uso terapéutico , Aspirina/uso terapéutico , Carragenina , Dexametasona/uso terapéutico , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Indometacina/uso terapéutico , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Masculino , Ratas , Ratas EndogámicasRESUMEN
The distribution of liposomes prepared from total mouse liver lipids and containing (3H)-labelled platelet activation factor in mouse organs was studied. It was shown that the majority of intraperitoneally injected liposomes prepared from total mouse liver lipids were transported to mouse liver and spleen. The interaction of liposomes with spleen cells in vitro revealed that the affinity of liposomes prepared from total spleen macrophage or total spleen lymphocyte lipids for mouse spleen cells was much higher than that of liposomes prepared from a model lipid mixture. The liposome binding to isolated spleen macrophages or lymphocytes was much higher than the liposome uptake by these cells in the total population of mouse spleen cells.
Asunto(s)
Linfocitos B/metabolismo , Metabolismo de los Lípidos , Liposomas , Hígado/metabolismo , Macrófagos/metabolismo , Linfocitos T/metabolismo , Animales , Ratones , Factor de Activación Plaquetaria/metabolismo , Bazo/citologíaRESUMEN
The influence of the phospholipid platelet activation factor (PAF) was studied on pokeweed mitogen (PWM)-stimulated proliferation of peripheral blood lymphocytes in patients with bronchial asthma and normal subjects. It was found that PAF exerts dose-dependent activation with following suppression mainly on B-cells after its action on the whole population of lymphocytes activated by PWM. Besides, the influence of PAF on lymphocyte proliferation seemed to be mediated by monocytes since removal of monocytes from the whole population of mononuclear cells abolished the lymphocyte activation induced by PWM. Indomethacin inhibits lymphocyte proliferation activation induced by PAF. The results indicate that PAF has an effect on the IgE and IgG synthesis by blood B-lymphocytes in patients with bronchial asthma.