Paf is thought to be involved in directing the movement migration of nerve cells neurons, a process. Full text full text is available as a scanned copy of the original print version. A factor which, like prostaglandins and leukotrienes, is released from cell membranes. Open access increased platelet activating factor levels in. Merge merge t t merge merge merge pdgfa pdgfb pdgfc pdgfd pdgfr fold expression relative to d0. Multiple substances stimulate its production, including lipopolysaccharide and tissue factors released after endothelial disruption. It is produced by a wide variety of cells including platelets, neutrophils, monocytesmacrophages, and endothelial cells. Platelet activating factor paf has been characterized as a new, ubiquitous. Paf is a phospholipid 10alkyl2acetylsnglycero3phosphorylcholine that has been implicated as a mediator in diverse pathologic processes. Plateletactivating factor and related lipid mediators annual.
Platelet activating factor and platelets springerlink. Emphasis is given on recent results about a new class of the socalled metalbased inhibitors of paf. 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. Platelets interact with several coagulation factors, while the coagulation product thrombin is a potent platelet activating agonist. 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. The ginsenosides are also believed to have the potential to inhibit platelet activating factor. Platelet activating factor paf, 1oalkyl2acetylsnglycero3phosphocholine is a biologically active phospholipid mediator. However, we found that the paf made by endothelial cells is. The nitric oxide and reactive oxygen species can combine to form a. Plateletactivating factor acetylhydrolases pafahs are unique pla2s which hydrolyze the sn2 ester linkage in. Vascular permeability of the conjunctiva was determined by measuring the. 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. Paf is able to induce key pathogenic features of asthma and to influence the activity of cells involved in immuneinflammatory process. Probing the substrate specificity of the intracellular brain platelet.
Platelet activating factor is a weak platelet agonist. Synthesis of plateletactivating factor by endothelial cells. Paf was discovered in 1972 as a fluidphase mediator released from igestimulated basophils that induce the aggregation of rabbit platelets. Paf is not stored but is rapidly generated via enzymatic acetylation of the precursor 1 o hexadecyl2hydroxy sn glycero3phosphocholine lysopaf.
Sano, novel agents combining platelet activating factor paf receptor. Usa home product directory cell biology cell signaling and neuroscience lipids in cell signaling platelet activating factors attention. Mechanisms of plateletactivating factor pafmediated. Demonstration that plateletactivating factor is capable. 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. At first, results of organic compounds natural and synthetic ones and specific and nonspecific as inhibitors of paf are reported. May 12, 2014 platelet activating factor pafplatelet activating factor paf introductionintroduction chemical and structural formulaechemical and structural formulae significancesignificance synthesis and metabolism.
This period saw a burst in research activity focused predominantly on the effect of paf in various organs. Role of the plateletactivating factor in inflammation. This complex regulates the amount of a molecule called platelet activating factor paf in the brain. 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. In 1972, the term plateletactivating factor paf was coined by. Degradation of paf by paf acetylhydrolase pafah has been shown to be associated with anaphylaxis, asthma, and peanut allergy. 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. The effect of paf and its antagonists was further intensively studied in vitro on isolated platelets, leucocytes, macrophages and endothelial cells. It is one of several paf acetylhydrolases function. Platelet activating factor is not constitutively pro duced by the endothelial cell but is rapidly synthesized upon appropriate stimulation 11, 12. Chemistry several molecular species of plateletactivating factor have been identified which vary in the length of the oalkyl side chain.
Platelet activating factor paf is a potent phospholipid mediator with pleiotropic effects. The first involves the release of adp and is inhibited by its conversion to atp by. Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet activating factor skip to main content thank you for visiting. The platelet activating factor paf signaling cascade in.
Platelet aggregation is mediated by at least three distinct mechanisms1,2. Receptorindependent metabolism of platelet activating factor by myelogenous cells joseph t. Meaning of platelet activating factor as a legal term. 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. 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. Chabot, jimmy redman, jr, david jacobson and robert l.
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. It is a potent cause of inflammation and an activator of several cell types of the immune system. In contrast, there have been few reports ofits effects oneosinophils. Sudden release of platelet activating factor paf into the circulation can cause hypotension, tachycardia, and circulatory collapse. Plateletactivating factor paf is a potent, bioactive phospholipid that acts on multiple cells and tissues through its g proteincoupled receptor gpcr. 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 paf, 10alkyl2acetylsnglycero3phosphocholine is a potent mediator of inflammation that causes neutrophil activation, increased vascular permeability, vasodilation, and bronchoconstriction in addition to platelet activation. 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. Platelet activating factor acetylglyceryletherphosphorylcholine. Platelet activating factor receptor the platelet activating factor receptor is a gprotein coupled receptor which binds platelet activating factor. Hormones that elicit paf synthesis include inflammatory agents such as histamine, thrombin, and bradykinin and vasoactive hormones such as angiotensin ii. Plateletactivating factor paf in allergic rhinitis. Targetspecific elisa kits are available from a variety of manufacturers. Plateletactivating factor medical definition merriam. Plateletactivating factor paf definition of platelet. However, little is known about the ability of paf to influence mast cell function directly. Plateletactivating factor an overview sciencedirect topics. Platelets interact with several coagulation factors, while the coagulation product thrombin is a potent plateletactivating agonist.
The platelet activating factor paf is an endogenous lipid mediator derived from membrane phospholipids. Plateletactivating factor paf is an important mediator. Fluid shear stress increases neutrophil activation via platelet activating factor michael j. Receptorindependent metabolism of plateletactivating factor. 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. Forty years since the structural elucidation of plateletactivating. Plateletactivating factor financial definition of platelet. Platelet activating factor, structure, and activity. Arecent study has suggested that it mayenhance leukotriene c4ltc4releasefromeosinophils14, andinanimalmodels, inhalation ofpafhascaused anincrease in the percentage of. In cardiovascular system, paf has been shown to have an important role in platelet and neutrophil aggregation, vascular. 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.
Coagulation factors, phosphatidylserine, platelet receptors, thrombin summary platelet activation and blood coagulation are complementary, mutually dependent processes in haemostasis and thrombosis. Since its discovery, the structure of plateletactivating factor paf also. Plateletactivating factor pafantagonists of natural. Platelet activating factor paf,1 thealkoxyetherlipid ioalkyl2acetylsnglyceryl3phosphocholine, wasoriginally describedasalipidlike factororiginatingfromigesensitized rabbit basophils that induced rabbit platelet aggregation and release 4. We asked whether paf possesses pyrogenic activity expt 1 and mediates lps fever expt 2. Plateletactivating factor alkylpaf is a potent inflammatory mediator. Definition of platelet, 4 factor in the financial dictionary by free online english dictionary and encyclopedia. Plateletactivating factor an overview sciencedirect. Platelet activating factor paf is a lipid mediator involved in several allergic reactions. Expression of adhesion molecules, plateletactivating factor. All corals pictures were taken with a gopro underwater camera, merged into a 3d model coral interactions and controls using autodesk 123d c. Importantly, it participates in a wide range of pathophysiological conditions. Increased platelet activating factor levels in chronic.
Plateletactivating factor receptor introduction bps. Plateletactivating factor and the release of a platelet. 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. Pafsynthesis has since been reported upon appropriate. Wykle departments of medicine and biochemistry, wake forest university medical center, winstonsalem, nc 27103, usa received 15 april 1989. Jcm free fulltext plateletactivating factor paf in. Paf is synthesized by several types of cells, including platelets, monocytes, macrophages, foam cells and endothelial cells upon activation. Platelet activating factor receptor antagonists improve the efficacy of. 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. Its alkyl group is connected by an ether linkage at the c1 carbon to a sixteen carbon chain.
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. To further examine this response, we performed detailed studies of cardiovascular function after paf administration. Platelet activating factor paf, a phospholipid with potent and diverse physiological and pathophysiological actions, is a powerful inducer of cell differentiation in herpetomonas muscarum. Abstract plateletactivating factor paf is a phospholipid with potent, diverse physiological actions, particularly as a mediator of inflammation. Platelet, 4 factor financial definition of platelet, 4 factor. Platelet factor 4 pf4, a 30 kilodalton, highaffinity heparinbinding protein, is produced in megakaryocytes and stored in platelet alpha granules. 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. A minute, nonnucleated, disklike cytoplasmic body found in the blood plasma of mammals that is derived from a megakaryocyte and functions to promote. Incorporation of3hacetate into a polar lipid is depen dentontheconcentration ofthrombin. Paf was originally described as a soluble factor in blood, so it is apparent that some cells secrete it following synthesis. Platelet activating factor synonyms, platelet activating factor pronunciation, platelet activating factor translation, english dictionary definition of platelet activating factor.
The lipidic molecule platelet activating factor paf sparks a wide range of immunoregulatory actions. Paf is formed by a smaller number of cell types than the eicosanoids, mainly. Plateletactivating factor and liver metastasis of colorectal. Role of platelet activating factor paf in the intestinal epithelial secretory and chinese hamster ovary cho cell cytoskeletal responses to cholera toxin. Platelet activating factors lipids in cell signaling.
Platelet activating factor acetylhydrolase 2, cytoplasmic is an enzyme that in humans is encoded by the pafah2 gene. Summary platelet activating factor paf is a potent pro. Detection of other special sample please contact our technical support. A phospholipid released by leukocytes that causes aggregation of platelets and other effects, such as an increase in vascular permeability and. As a consequence, the nursing neonates suffer from alopecia, anaemia and growth. Find out information about platelet activating factor. 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 an endogenous, active phospholipid released from inflammatory cells, platelets, and endothelial cells, and is involved in the regulation of immune responses. General characteristics of the platelet activating factor. In this study we examine the ability of paf to activate mast cells and regulate mast cell chemotaxis. 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. The role of platelet activating factor paf as a mediator of increased conjunctival vascular permeability was investigated in a guineapig model of immediate hypersensitivity. 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.
This gene encodes a seventransmembrane gproteincoupled receptor for platelet activating factor paf that localizes to lipid rafts andor caveolae in the cell membrane. Opposing effects of plateletactivating factor and lyso. Pdf cardiovascular effects of plateletactivating factor. Definition of platelet activating factor in the legal dictionary by free online english dictionary and encyclopedia. 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. Paf is formed by a smaller number of cell types than the eicosanoids, mainly leukocytes, platelets, and endothelial cells. 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. 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. Platelet activating factors are associated with depressive. Physiological and pathophysiological effects of paf. Jan 17, 2015 platelet activating factors by aisha siddiqui 1. Pdf forty years since the structural elucidation of platelet.
Plateletactivating factor paf is generated in a variety of inflammatory conditions in which mast cells accumulate. Macrophage vldl receptor promotes pafah secretion in. Briefly, lysopc was acylated by combining 1 mg of lysopc with acetic. Here, we note that combining chemo and radiotherapy with platelet activating factor antagonists could be a promising strategy for cancer. Plateletactivating factor proceedings ofthe second national heart and lunginstitute workshop, held on 1 july 1988 at the national heart and lunginstitute, london platelet activatingfactor. These early studies demonstrated that paf is released directly from cell membranes and mediates a. Paf is a potent proinflammatory mediator which plays a role in different inflammatory diseases, including bronchial asthma. Administration of paf can produce many of the symptoms observed in asthma, probably via the formation of leukotrienes as secondary mediators. Streptococcus pneumoniae anchor to activated human cells. Get a printable copy pdf file of the complete article 316k, or click on a page image below to browse page by page. Platelet activating factor paf platelet activating factor paf introductionintroduction chemical and structural formulaechemical and structural formulae significancesignificance synthesis and metabolism. Platelet activating factor a molecular link between.
Pdf in the late 1960s, barbaro and zvaifler described a substance that caused. Platelet activating factor paf is a potent proinflammatory negotiator that shows distinct spectrum of biological and pharmacological effects. Plateletactivating factor legal definition of platelet. Fluid shear stress increases neutrophil activation via. That paf possesses hypothermic activity and mediates lps. Pdf the role of plateletactivating factor in sepsis. Endothelialcells werestimu lated for 5 minwith thrombin at various concentrations. Paf 10alkyl2acetylsnglycero3phosphorylcholine is a phospholipid that plays a significant role in oncogenic transformation, tumor growth, angiogenesis.
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