Jan 17, 2015 platelet activating factor, also known as paf, paf acether or agepc acetylglyceryletherphosphorylcholine, is a potent phospholipid activator and mediator of many leukocyte functions, including platelet aggregation and degranulation, inflammation, and anaphylaxis. Platelet activating factor antagonists and implantation in rabbits. Platelet activating factor paf receptor antagonists were recently demonstrated to have effective pain relieving effects on neuropathic pain in several animal models. Pdf role of plateletactivating factor in cardiovascular. Paf is a phospholipid 10alkyl2acetylsnglycero3phosphorylcholine that has been implicated as a mediator in diverse pathologic processes. Plasmalogens, platelet activating factor and beyond ether lipids in signaling and neurodegeneration. Platelet activating factor stimulates sodiumproton exchange. These results suggest that platelet activating factor is involved in the accumulation of pmn in the reperfused ischemic myocardium and contributes to the evolution of myocardial injury. Download fulltext pdf download fulltext pdf download fulltext pdf read full.
Platelet aggregation is mediated by at least three distinct mechanisms1,2. Transplantation original article changes in glomerular. In this study, patients with anaphylactic reactions were found to have. Jcm free fulltext plateletactivating factor paf in. Abstractwe studied the expression of lipoproteinassociated phospholipase a 2 lppla 2, an enzyme capable of hydrolyzing platelet activating factor paf, paflike phospholipids, and polarmodified phosphatidylcholines, in human and rabbit atherosclerotic lesions.
Plateletactivating factor is a phospholipid with diverse. Platelet activating factor acetylhydrolase 2, cytoplasmic is an enzyme that in humans is encoded by the pafah2 gene. Platelet activating factor enhances in vitro fertilization of. Whatever the site of the biopsy, the level of platelet activating factor in colonic mucosa was higher p platelet aggregation in vivo in rabbits and dogs. Plateletactivating factor and human thyroid cancer in. Plateletactivating factor legal definition of platelet. Activation of platelet function through g proteincoupled. Plateletactivating factor, paf acetylhydrolase, and severe. Platelet activating factor paf is the commonly used name for a group of potent. The present study examined the pain relieving effect of paf receptor antagonists on bone cancer pain using the femur bone cancer fbc model in mice.
Plateletactivating factor paf is a phospholipid mediator that belongs to a family. We measured paf levels free, bound and total in blood and we studied. Full text get a printable copy pdf file of the complete article 2. The platelet activating factor paf 1oalkyl2acetylsnglycero3phosphocholine is a potent lipid first messenger active in general cell activation, fertilization, inflammatory and allergic reactions, asthma, hiv pathogenesis, carcinogenesis, and apoptosis. Human plasma platelet activating factor acetylhydrolase. Quillen platelet activating factor paf 1oalkyl20acetylcollege of medicine, east tennessee state unive rsity. Pdf plateletactivating factor significantly enhances. Platelet activating factor is a prominent the first 120 min of e. Plateletactivating factor, paf acetylhydrolase, and. Platelet activating factor, lyso platelet activating factor, and alkyl acyl glycerophosphocholine were found in patients with acute crohns disease and in remission as well as in controls. Role of plateletactivating factor in hepatocellular ca2. Amantadine inhibits platelet activating factor induced clathrinmediated endocytosis in human neutrophils phillip c.
Understanding and evaluating platelet function hematology. Palliation of bone cancer pain by antagonists of platelet. It is also involved in changes to vascular permeability, the oxidative burst, chemotaxis of leukocytes, as well as augmentation of. Plateletactivating factor an overview sciencedirect. Plateletactivating factor and related lipid mediators f. Plateletactivating factor an overview sciencedirect topics. The plateletactivating factor receptor is a gprotein coupled receptor which binds platelet activating factor the paf receptor shows structural characteristics of the rhodopsin mim 180380 gene family and binds platelet activating factor paf. Plateletactivating factor stimulates sodiumhydrogen. Platelet activating factor paf is the most potent phospholipid agonist known to date.
Common and distinct intracellular signaling pathways in human neutrophils utilized by platelet activating factor and fmlp. Platelet activating factor paf is a phospholipid that has been implicated in the pathogenesis of glomerulonephritis and can be synthesized by. This chemokine is released from alphagranules of activated platelets during platelet aggregation, and promotes blood coagulation by moderating the effects of heparinlike molecules. Pdf urinary excretion of plateletactivating factor in.
Platelet activating factor, intrauterine insemination, sperm, pregnancy received august 11, 2003. Pdf platelet activating factor paf is a phospholipid mediator that belongs to a family of biologically active. Download fulltext pdf download fulltext pdf read fulltext. Plateletactivating factor, also known as paf, pafacether or agepc acetylglyceryletherphosphorylcholine, is a potent phospholipid activator and mediator of many leukocyte functions, platelet aggregation and degranulation, inflammation, and anaphylaxis. Spitzer1 1nora eccles harrison cardiovascular research and training institute and department of physiology and 2huntsman cancer institute and department of internal medicine, university of utah, salt lake city, utah. Thus, the paf signaling system is a point of convergence at which. Plateletactivating factor and the release of a platelet. The capacity of plateletactivating factor paf to stimulate its own synthesis by. In vivo, uncontrolled free radical reactions generate large amounts of paflike oxidized. Plateletactivating factor paf is a phospholipid with potent, diverse physiological actions, particularly as a mediator of inflammation. Harper department of obstetrics and gynecology, university of texas health science center, san antonio, tx 782847836 usa in an initial experiment, rabbits were injected i. Before the onset of hus, patients with e coli o157.
Platelet activating factor paf is a potent phospholipid mediator that was first described by its. Pdf plateletactivating factor and related lipid mediators. The intracoronary artery injection of platelet rich plasma activated with platelet activating factor into thrombocytopenic dogs produced a significantly greater increase in coronary artery blood flow than the injection of either nonactivated platelet rich plasma or platelet depleted plasma to which platelet activating factor was added. Platelet activating factor produced in vitro by kaposis sarcoma cells induces and sustains in vivo angiogenesis. Pmns isolated from healthy human donors were incubated with il6 0. Accurate quantitation of paf has always been difficult because of the physicochemical properties of paf and its structural similarity to several much more abundant phospholipids. Factor an event, circumstance, influence, or element that plays a part in bringing about a result. Platelet activating factor and platelets springerlink.
Transplantation original article changes in glomerular cross. Platelet factor 4 pf4 is a small cytokine belonging to the cxc chemokine family that is also known as chemokine cxc motif ligand 4 cxcl4. The present study examined the pain relieving effect of paf receptor antagonists on bone cancer pain using the. Oxidative modification of lowdensity lipoprotein, which plays an important role in atherogenesis, generates biologically. This gene encodes platelet activating factor acetylhydrolase isoform 2, a singlesubunit intracellular enzyme that catalyzes the removal of the acetyl group at the sn2 position of platelet activating factor identified as 1. The plateletactivating factor signaling system and its regu. Jan 01, 2007 plateletactivating factor paf is a potent mediator that occurs at very low concentrations in cells and tissues. Platelet activating factor in allergies krzysztof palgan, zbigniew. Pdf plateletactivating factor antagonists and implantation. Platelet activating factor paf is an endogenous phospholipid involved in platelet.
Platelet activating factor paf represents an important component of these inflammatory cascades, and we have examined the influence of a specific paf receptor antagonist sri 63441 on the inhibition of hyperacute rejection in two experimental models, the rejection of rat cardiac allografts by presensitized recipients and guinea pigtorat. Paf stimulates nhe in neutrophils and platelets, but its effect on cardiac nhe nhe1 is resolved. Picomolar platelet activating factor mobilizes ca to change platelet shape without activating phospholipase c or protein kinase c. On the other hand the pivotal role of plateletactivating factor paf. Biochemistry, platelet activating factor statpearls ncbi bookshelf. Platelet activating factor levels and metabolism in tangier disease. Platelet activating factor antagonists and implantation in rabbits c.
Raised concentrations of platelet activating factor in. The synthesis, transport, and degradation of paf are. Pdf plateletactivating factor and human meningiomas. The first step is the transfer acetyl residue onto a phospholipid, alkyllysoglycerophosphate. Characterization of plateletactivating factorinduced. In fact, re1 and the free ligand exhibit the same inhibitory effect, while reco5cl does not seem.
Recently, wehave found that il6 suppresses pmn apoptosis via apaflike mechanism. Pdf plateletactivating factor and bacteremiainduced. We have studied the metabolic and functional effects of two new platelet. Platelet activation and the formation of the platelet plug. Thrombopoietin stimulates endothelial cell motility and. Platelet reactivity mediators stimulate the release of inflammatory eicosanoids and tumor necrosis factor tnf. Plateletactivating factor does not stimulate camp formation. Plateletactivating factor acetylhydrolases journal of biological. Pdf plateletactivating factor pafantagonists of natural. A factor in a case contributes to its causation or outcome. The possible involvement of platelet activating factor paf in the pathogenesis of endotoxemia, was investigated by using a binding assay to patients platelets, complemented with the extraction and chemical characterization of paf obtained from patients platelets. Platelet activating factor acetylglyceryletherphosphorylcholine.
Upon cell activation, the action of lipases on membrane phospholipids produces free fatty acids and the phospholipid backbone. Platelet activating factor and bacteremiainduced pulmonary hypertension. Paf is a potent and versatile mediator of inflammation that is produced by numerous cell types and tissues, particularly by leukocytes. Platelet activating factor, in vitro fertilization fromthedepartmentofobstetmsand gynecology,jamesh. Researchers discover novel therapeutic strategy for. Ldl from free radical oxidation, thus playing an anti. Jcm free fulltext plateletactivating factor paf in allergic. Recovery of postischemic brain metabolism and function.
Plateletactivating factor paf is a phospholipid produced by a variety of cells including platelets, endothelial cells, neutrophils, monocytes and macrophages. Pdf plasmalogens, plateletactivating factor and beyond. Effects of salbutamol on bronchoconstriction, bronchial hyperresponsiveness, and leucocyte responses induced by platelet activating factor in man. Free radical reactions are not constrained by the pauli exclusion. Among the former are eicosanoids prostaglandins and leukotrienes. The role of plateletactivating factor in platelet aggregation nature. Plateletactivating factor paf stimulates a diverse array of cellular responses. This leads to more paf release from the cells and causes increased platelet activation. This study characterized the nature of the response to platelet activating factor paf in the cerebral microcirculation of the newborn pig.
J a nick, n j avdi, s k young, c knall, p gerwins, g l johnson, and g s worthen. Platelet activating factor paf is a low molecular weight, etherlinked phospholipid originally identified as a soluble factor, released from sensitized rabbit basophils during ige anaphylaxis, that was capable of aggregating rabbit platelets 1, 2. Platelet activating factor enhances in vitro fertilization. Platelet activating factor induces expres growth by altering the local angiogenic and cytokine net sion of early response genes cfos and tis1 in human works as previously suggested for breast and. The most potent trigger of platelets known, is the lipid inflammatory molecule, platelet activating factor paf discovered in 1972. The discovery of platelet activating factor antagonists paf antagonists during these decades are going on with different framework, but the researchers. Role of plateletactivating factor in polymorphonuclear.
Plateletactivating factor paf is an anaphylactic mediator that is degraded in the blood by the enzyme paf acetylhydrolase. Whatever the site of the biopsy, the level of platelet activating factor in colonic mucosa was higher p platelet activating factor in man. Effect of platelet activating factor acetylhydrolase on the formation and action of minimally oxidized low density lipoprotein. Paf is considered a potential relevant mediator in allergic rhinitis, with a key. Platelet activating factor produced by platelets, endothelial cells, leukocytes functions. In many centers druginduced ovulation iui cycles followed by. Platelet activating factor induces expres growth by altering the local angiogenic and cytokine net sion of early response genes cfos and tis. In the canine model, paf appears to become more important after leukocyte infiltration of the arterial wall, as it may contribute to initiating enough platelet activation to lead to cyclic flow variations at sites of arterial stenosis and endothelial injury. Platelet activating factor paf, 1oalkyl2acetylsnglycero3phosphocholine is a potent proinflammatory phospholipid that is released in the heart in response to oxidative. The role of platelet activating factor in allergic. Platelet activating factor paf has been characterized as a new, ubiquitous, potent, and unique class of.
Pdf amantadine inhibits plateletactivating factor induced. Occupancy of platelet receptors for plateletactivating. Platelet activating factor paf is a phospholipid that has been implicated in the pathogenesis of glomerulonephritis and can be synthesized by glomerular cells in response to different stimuli. It is released from multiple cells of the immune system, such as eosinophils, neutrophils, and mast cells, and also exerts its effect on most of them upon specific binding to its receptor, becoming a pleiotropic mediator. Summary platelet activating factor paf is a potent pro. It is one of several paf acetylhydrolases function. We hypothesized that il6 stimulates pmns toproduce paf. Pdf platelet activating factor stimulates sodiumproton. Data extraction, synthesis, and summary paf, a phospholipid signaling molecule, transmits outsidein signals to intracellular transduction systems and effector mechanisms in a variety of cell types, including key cells of the innate immune and hemostatic systems. The platelet activating factor paf produced and released by mast cells, basophils, neutrophils, eosinophils, fibroblasts, platelets, endothelial. Synthesis of plateletactivating factor by human monocytes.
Jci common and distinct intracellular signaling pathways. Platelet activating factor paf is a lipid mediator involved in several allergic reactions. Expression of platelet activating factor receptor transcript1 but not transcript2 by human bone marrow cells. Lipoproteinassociated phospholipase a2, plateletactivating. Effects of platelet activating factor on airway calibre, airway responsiveness, and circulating cells in asthmatic subjects. Platelet activating factor is a phospholipid with diverse. We recently demonstrated virtual absence of plasmalogentype. The first involves the release of adp and is inhibited by its. Blood gases, eeg, auditory evoked potentials, cerebral metabolic rate for glucose cmr glc, and cerebral metabolic rate for oxygen cmro 2. Role of plateletactivating factor in cardiovascular pathophysiology. Platelet activating factor stimulates sodiumhydrogen exchange in ventricular myocytes yoichi ajiro,1 noriko saegusa,1 wayne r.
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