Mechanisms of plateletactivating factor pafmediated. May 12, 2014 platelet activating factor pafplatelet activating factor paf introductionintroduction chemical and structural formulaechemical and structural formulae significancesignificance synthesis and metabolism. Targetspecific elisa kits are available from a variety of manufacturers. General characteristics of the platelet activating factor. Platelets interact with several coagulation factors, while the coagulation product thrombin is a potent platelet activating agonist. Probing the substrate specificity of the intracellular brain platelet. Paf is a phospholipid 10alkyl2acetylsnglycero3phosphorylcholine that has been implicated as a mediator in diverse pathologic processes. Endothelialcells werestimu lated for 5 minwith thrombin at various concentrations. Physiological and pathophysiological effects of paf.
Wykle departments of medicine and biochemistry, wake forest university medical center, winstonsalem, nc 27103, usa received 15 april 1989. Synthesis of plateletactivating factor by endothelial cells. Plateletactivating factor and liver metastasis of colorectal. A minute, nonnucleated, disklike cytoplasmic body found in the blood plasma of mammals that is derived from a megakaryocyte and functions to promote. Paf is not stored but is rapidly generated via enzymatic acetylation of the precursor 1 o hexadecyl2hydroxy sn glycero3phosphocholine lysopaf. Role of the plateletactivating factor in inflammation. The nitric oxide and reactive oxygen species can combine to form a.
This complex regulates the amount of a molecule called platelet activating factor paf in the brain. Usa home product directory cell biology cell signaling and neuroscience lipids in cell signaling platelet activating factors attention. Plateletactivating factor paf is an important mediator. Platelet activating factor paf is an endogenous, active phospholipid released from inflammatory cells, platelets, and endothelial cells, and is involved in the regulation of immune responses. Open access increased platelet activating factor levels in. As a consequence, the nursing neonates suffer from alopecia, anaemia and growth.
Paf was discovered in 1972 as a fluidphase mediator released from igestimulated basophils that induce the aggregation of rabbit platelets. Fluid shear stress increases neutrophil activation via platelet activating factor michael j. Increased platelet activating factor levels in chronic. Platelet activating factor receptor antagonists improve the efficacy of. Demonstration that plateletactivating factor is capable. 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. Plateletactivating factor legal definition of platelet. Here, we note that combining chemo and radiotherapy with platelet activating factor antagonists could be a promising strategy for cancer. Plateletactivating factor acetylhydrolases pafahs are unique pla2s which hydrolyze the sn2 ester linkage in. 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. This gene encodes a seventransmembrane gproteincoupled receptor for platelet activating factor paf that localizes to lipid rafts andor caveolae in the cell membrane. Platelet factor 4 pf4, a 30 kilodalton, highaffinity heparinbinding protein, is produced in megakaryocytes and stored in platelet alpha granules.
Platelet activating factor paf is a potent inflammatory mediator that mimics many of the features of asthma, including eosinophil recruitment and activation and induction of ahr. Plateletactivating factor pafantagonists of natural. Definition of platelet, 4 factor in the financial dictionary by free online english dictionary and encyclopedia. In relation to asthma, platelet activating factor is able to act directly as a chemotactic factor and indirectly by stimulating the release of other inflammatory agents. Paf acts by binding to a unique g proteincoupled seven transmembrane receptor pafr and activates multiple intracellular signalling pathways by coupling to the g q11 and g io families of g proteins. The first involves the release of adp and is inhibited by its conversion to atp by. Platelet activating factor paf is a potent proinflammatory negotiator that shows distinct spectrum of biological and pharmacological effects. Importantly, it participates in a wide range of pathophysiological conditions. Platelet activating factor is not constitutively pro duced by the endothelial cell but is rapidly synthesized upon appropriate stimulation 11, 12. Plateletactivating factor paf in allergic rhinitis. The lipidic molecule platelet activating factor paf sparks a wide range of immunoregulatory actions.
A factor which, like prostaglandins and leukotrienes, is released from cell membranes. Platelet activating factors lipids in cell signaling. It is released from multiple cells of the immune system, such as eosinophils, neutrophils, and mast cells, and also exerts its e ect on most of them upon speci. Platelet activating factors are associated with depressive. Sudden release of platelet activating factor paf into the circulation can cause hypotension, tachycardia, and circulatory collapse. Platelet activating factor paf, a phospholipid with potent and diverse physiological and pathophysiological actions, is a powerful inducer of cell differentiation in herpetomonas muscarum. Plateletactivating factor paf is generated in a variety of inflammatory conditions in which mast cells accumulate. Definition of platelet activating factor in the legal dictionary by free online english dictionary and encyclopedia. In cardiovascular system, paf has been shown to have an important role in platelet and neutrophil aggregation, vascular. Chabot, jimmy redman, jr, david jacobson and robert l. Plateletactivating factor receptor introduction bps. 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. Multiple substances stimulate its production, including lipopolysaccharide and tissue factors released after endothelial disruption. The role of platelet activating factor paf as a mediator of increased conjunctival vascular permeability was investigated in a guineapig model of immediate hypersensitivity.
Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet activating factor skip to main content thank you for visiting. Platelet activating 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. Plateletactivating factor and the release of a platelet. Plateletactivating factor an overview sciencedirect. Platelet activating factor receptor the platelet activating factor receptor is a gprotein coupled receptor which binds platelet activating factor. It is a potent cause of inflammation and an activator of several cell types of the immune system. Platelet activating factor paf has been characterized as a new, ubiquitous. Platelets interact with several coagulation factors, while the coagulation product thrombin is a potent plateletactivating agonist. Its alkyl group is connected by an ether linkage at the c1 carbon to a sixteen carbon chain. Forty years since the structural elucidation of plateletactivating. The single plateletactivating factor receptor pafr is a gprotein coupled receptor present in the plasma and nuclear membranes of the majority of cells of the vascular and innate immune system that activates a variety of pathways involved in inflammation, oncogenic transformation, tumor growth, angiogenesis and metastasis. Pdf in the late 1960s, barbaro and zvaifler described a substance that caused. The ginsenosides are also believed to have the potential to inhibit platelet activating factor. Plateletactivating factor paf is a potent, bioactive phospholipid that acts on multiple cells and tissues through its g proteincoupled receptor gpcr.
We asked whether paf possesses pyrogenic activity expt 1 and mediates lps fever expt 2. Emphasis is given on recent results about a new class of the socalled metalbased inhibitors of paf. To further examine this response, we performed detailed studies of cardiovascular function after paf administration. Following the identification of platelet activating factor paf in 1972, and structural confirmation in 1979, there was intense interest in the biology of this phospholipid. Get a printable copy pdf file of the complete article 316k, or click on a page image below to browse page by page. Plateletactivating factor paf is a potent inflammatory mediator that mimics many of the features of asthma, including eosinophil recruitment and activation and induction of ahr. However, we found that the paf made by endothelial cells is. Role of platelet activating factor paf in the intestinal epithelial secretory and chinese hamster ovary cho cell cytoskeletal responses to cholera toxin. Paf was originally described as a soluble factor in blood, so it is apparent that some cells secrete it following synthesis. Jcm free fulltext plateletactivating factor paf in. The platelet activating factor paf is an endogenous lipid mediator derived from membrane phospholipids. Certain features of will be unavailable due to maintenance from saturday evening, march 21st at 8. Plateletactivating factor alkylpaf is a potent inflammatory mediator. Plateletactivating factor receptor pafr is a g q g 11coupledprotein receptor that has a role in a wide range of biological processes such as vasodilation, superoxide formation, cell proliferation, angiogenesis and regulation of the inflammatory response.
Meaning of platelet activating factor as a legal term. Platelet, 4 factor financial definition of platelet, 4 factor. 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. Streptococcus pneumoniae anchor to activated human cells. Plateletactivating factor and related lipid mediators annual. Plateletactivating factor is a phospholipid with diverse. Pdf the role of plateletactivating factor in sepsis. A phospholipid released by leukocytes that causes aggregation of platelets and other effects, such as an increase in vascular permeability and. In this study we examine the ability of paf to activate mast cells and regulate mast cell chemotaxis. Find out information about platelet activating factor. Platelet activating factor paf, 10alkyl2acetylsnglycero3phosphocholine is a potent mediator of inflammation that causes neutrophil activation, increased vascular permeability, vasodilation, and bronchoconstriction in addition to platelet activation. By continuing to use our website, you are agreeing to our use of cookies.
Pdf forty years since the structural elucidation of platelet. Receptorindependent metabolism of platelet activating factor by myelogenous cells joseph t. Pdf cardiovascular effects of plateletactivating factor. Platelet activating factor, structure, and activity. Expression of adhesion molecules, plateletactivating factor. Plateletactivating factor financial definition of platelet. It is one of several paf acetylhydrolases function. Platelet activating factor paf lipids, which are associated with cad, have recently been linked with novel proposed etiopathological mechanisms for depression such as inflammation, oxidativenitrosative stress, and vascular endothelial dysfunction. Chemistry several molecular species of plateletactivating factor have been identified which vary in the length of the oalkyl side chain. Paf is formed by a smaller number of cell types than the eicosanoids, mainly leukocytes, platelets, and endothelial cells. Coagulation factors, phosphatidylserine, platelet receptors, thrombin summary platelet activation and blood coagulation are complementary, mutually dependent processes in haemostasis and thrombosis.
The pafah1b1 gene also known as lis1 provides instructions for making a protein that is one part subunit of a complex called platelet activating factor acetyl hydrolase 1b pafah1b. Full text full text is available as a scanned copy of the original print version. Platelet activating factor a molecular link between. Administration of paf can produce many of the symptoms observed in asthma, probably via the formation of leukotrienes as secondary mediators. However, little is known about the ability of paf to influence mast cell function directly. Detection of other special sample please contact our technical support. Platelet activating factor acetylhydrolase 2, cytoplasmic is an enzyme that in humans is encoded by the pafah2 gene. Pafsynthesis has since been reported upon appropriate. Platelet activating factor paf has been characterized as a new, ubiquitous, potent, and unique class of lipid chemical mediators that share similar biological activities, namely, paflike activity molecules 1.
In contrast, there have been few reports ofits effects oneosinophils. Paf is synthesized by several types of cells, including platelets, monocytes, macrophages, foam cells and endothelial cells upon activation. The platelet activating 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. Platelet activating factor paf is a lipid mediator involved in several allergic reactions. Rat platelet activating factor paf elisa kit this product is suitable for in vitro quantitative detection of rat serum, plasma or cell culture supernatant and organizations in the natural and recombinant paf concentration. Paf is formed by a smaller number of cell types than the eicosanoids, mainly.
Paf is able to induce key pathogenic features of asthma and to influence the activity of cells involved in immuneinflammatory process. Since its discovery, the structure of plateletactivating factor paf also. Briefly, lysopc was acylated by combining 1 mg of lysopc with acetic. Plateletactivating factor medical definition merriam. Vascular permeability of the conjunctiva was determined by measuring the. Summary platelet activating factor paf is a potent pro. The plateletactivating factor paf signaling cascade consists of paf and paflike lipids pafll that are specific, structurallydefined ligands for a gprotein coupled receptor, the paf receptor pafr, which has restricted expression on key target cells of the inflammatory, immune, and hemostatic systems. Platelet activating factor paf,1 thealkoxyetherlipid ioalkyl2acetylsnglyceryl3phosphocholine, wasoriginally describedasalipidlike factororiginatingfromigesensitized rabbit basophils that induced rabbit platelet aggregation and release 4. All corals pictures were taken with a gopro underwater camera, merged into a 3d model coral interactions and controls using autodesk 123d c.
Platelet activating factor acetylglyceryletherphosphorylcholine. Platelet activating factor paf is a potent phospholipid mediator, which has previously reported biological activities in bc progression and osteoclast differentiation by activating its receptor. Supplier of assay kits, antibodies, biochemicals, and proteins and provider of contract research services. The single platelet activating factor receptor pafr is a gprotein coupled receptor present in the plasma and nuclear membranes of the majority of cells of the vascular and innate immune system that activates a variety of pathways involved in inflammation, oncogenic transformation, tumor growth, angiogenesis and metastasis. The platelet activating factor paf signaling cascade in. Opposing effects of plateletactivating factor and lyso. Platelet aggregation is mediated by at least three distinct mechanisms1,2. Hormones that elicit paf synthesis include inflammatory agents such as histamine, thrombin, and bradykinin and vasoactive hormones such as angiotensin ii. Platelet activating factor synonyms, platelet activating factor pronunciation, platelet activating factor translation, english dictionary definition of platelet activating factor. Platelet activating factor and platelets springerlink. Platelet activating factor paf is a potent phospholipid mediator with pleiotropic effects. At first, results of organic compounds natural and synthetic ones and specific and nonspecific as inhibitors of paf are reported. Degradation of paf by paf acetylhydrolase pafah has been shown to be associated with anaphylaxis, asthma, and peanut allergy.
In 1972, the term plateletactivating factor paf was coined by. Platelet activating factor paf, 1oalkyl2acetylsnglycero3phosphocholine is a biologically active phospholipid mediator. Macrophage vldl receptor promotes pafah secretion in. Plateletactivating factor paf definition of platelet. Plateletactivating factor an overview sciencedirect topics. Plateletactivating factor proceedings ofthe second national heart and lunginstitute workshop, held on 1 july 1988 at the national heart and lunginstitute, london platelet activatingfactor. The effect of paf and its antagonists was further intensively studied in vitro on isolated platelets, leucocytes, macrophages and endothelial cells. Abstract plateletactivating factor paf is a phospholipid with potent, diverse physiological actions, particularly as a mediator of inflammation. Platelet activating factor paf is a proinflammatory lipid mediator possessing a unique 1oalkyl glycerophospholipid gpc backbone ioalkyl2a we use cookies to enhance your experience on our website. Platelet activating factor is a weak platelet agonist. This period saw a burst in research activity focused predominantly on the effect of paf in various organs. Plateletactivating factoracether is a component of human. Paf 10alkyl2acetylsnglycero3phosphorylcholine is a phospholipid that plays a significant role in oncogenic transformation, tumor growth, angiogenesis. Merge merge t t merge merge merge pdgfa pdgfb pdgfc pdgfd pdgfr fold expression relative to d0.
Review mechanisms of plateletactivating factor paf mediated responses in the lung stefan uhlig, rolf goggel, stephanie engel division pulmonary pharmacology, research center borstel, leibnizcenter for medicine and biosciences. Factor, platelet activating phosphorylcholine, acetyl glyceryl ether platelet aggregating factor aggregating factor, platelet platelet aggregation enhancing factor agepc thrombocyte aggregating activity 1alkyl2acetylsnglycerophosphocholine 1 alkyl 2 acetyl sn glycerophosphocholine acetyl glyceryl ether. Paf is a potent proinflammatory mediator which plays a role in different inflammatory diseases, including bronchial asthma. Targetspecific elisa kits are available from a variety of manufacturers and can help streamline your immunodetection experiments. Platelet activating factor paf platelet activating factor paf introductionintroduction chemical and structural formulaechemical and structural formulae significancesignificance synthesis and metabolism. It is produced by a wide variety of cells including platelets, neutrophils, monocytesmacrophages, and endothelial cells.
Plateletactivating factor paf, 10alkyl2acetylsnglycero3phosphocholine is a potent mediator of inflammation that causes neutrophil activation, increased vascular permeability, vasodilation, and bronchoconstriction in addition to platelet activation. Fluid shear stress increases neutrophil activation via. Paf is thought to be involved in directing the movement migration of nerve cells neurons, a process. Arecent study has suggested that it mayenhance leukotriene c4ltc4releasefromeosinophils14, andinanimalmodels, inhalation ofpafhascaused anincrease in the percentage of. Jan 17, 2015 platelet activating factors by aisha siddiqui 1.
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