Disease relevance of PAF acether

• Platelet-activating factor (PAF), a unique phospholipid mediator, possesses potent proinflammatory, smooth-muscle contractile and hypotensive activities, and appears to be crucial in the pathogenesis of bronchial asthma and in the lethality of endotoxin and anaphylactic shock [1].
• Platelet-activating factor (PAF) induces pulmonary edema and has a key role in acute lung injury (ALI) [2].
• Injection of synthetic PAF-acether induces similar effects, including bronchoconstriction, respiratory arrest, systemic hypotension, neutropenia, and thrombocytopenia [3].
• Platelet-activating factor caused rapid pulmonary vasoconstriction and edema in isolated lungs perfused with albumin-free salt solution devoid of formed blood elements [4].
• However, PAF-acether is not responsible for the anaphylaxis-induced thrombocytopenia [3].

Psychiatry related information on PAF acether

• Platelet-activating factor antagonist BN52021 decreases accumulation of free polyunsaturated fatty acid in mouse brain during ischemia and electroconvulsive shock [5].
• BACKGROUND: Platelet-activating factor (PAF), a family of structurally-related phospholipid mediators of inflammation, is present in normal human mixed saliva; however, its role in oral biology and the homeostasis of oral host defense mechanisms remains to be established [6].
• PAF-acether (93 nM) and embryo-derived PAF of similar activity induced an identical time response of platelet aggregation, the response being maximal by 6 min [7].
• The aim of the study was to test the hypothesis that raised platelet-activating factor (PAF) may contribute to the aetiology of developmental dyslexia [8].
• Beside this bacosides also reversed BN52021 induced retrograde amnesia, probably due to increase in platelet activating factor (PAF) synthesis by enhancing cerebral glutamate level [9].

High impact information on PAF acether

• Cytosolic phospholipase A2 initiates the biosynthesis of prostaglandins, leukotrienes, and platelet-activating factor (PAF), mediators of the pathophysiology of asthma and arthritis [10].
• Platelet-activating factor as a potential retrograde messenger in CA1 hippocampal long-term potentiation [11].
• Role of platelet-activating factor-acether in mediating guinea pig anaphylaxis [3].
• Platelet-activating factor (PAF), a naturally occurring phospholipid, is a potent activator of various biological processes, including platelet aggregation [12].
• Inhibition of cPLA2, or blockade of the platelet-activating factor (PAF) receptor, blocked antigen-induced airway hyperresponsiveness and suppressed eosinophil infiltration [13].

Chemical compound and disease context of PAF acether

• Agents that interfere with PAF-induced ceramide synthesis, such as steroids or the xanthogenate D609, attenuate pulmonary edema formation induced by PAF, endotoxin or acid instillation [2].
• When challenged by external stimuli including cytokines and hypoxia, CEC have been shown to release/express various products of arachidonic acid cascade with both vasoactive and pro-inflammatory properties, including prostaglandins, leukotrienes, and platelet-activating factor (PAF) [14].
• The platelet activating factor (PAF) antagonist, WEB2086, and a tumor necrosis factor (TNF)-alpha-specific antibody were also effective in attenuating the gut I/R-induced leukostasis and NAD(P)H autofluorescence [15].
• Phenidone (10 mg/kg), a dual cyclooxygenase/5-lipoxygenase inhibitor, affected neither the neutropenia nor the neutrophilia induced by C5a, f-MLF, or PAF [16].
• Although unable to inhibit cAMP formation in intact platelets, both PAF and vasopressin caused pertussis toxin-sensitive inhibition of adenylyl cyclase in isolated membranes [17].

Biological context of PAF acether

• It was shown that PAF-acether elicited both chemotaxis and chemokinesis of eosinophils [18].
• Thrombin, basophil platelet-activating factor (PAF), or ionophore A23187 treatment of intact 32PO43--loaded rabbit platelets resulted in a 200-400% increase in phosphorylation of P7P and P9P, respectively [19].
• Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase [20].
• In analyzing possible differences in signal transduction between the immortalized NT and HT lymphoblasts, we observed that cell stimulation with PAF and somatostatin caused a twofold higher increase in [Ca2+]i in HT than in NT cell lines [21].
• BACKGROUND/AIMS: Platelet-activating factor (PAF) is an important mediator of proinflammatory cell-to-cell interactions with powerful vasoactive properties [22].

Anatomical context of PAF acether

• These data indicate that cells other than mast cells are sufficient to induce an IgE-dependent active fatal anaphylaxis by elaborating PAF, which is the critical mediator for fatal murine anaphylaxis [23].
• Activation and desensitization of platelets by platelet-activating factor (PAF) derived from IgE-sensitized basophils. I. Characteristics of the secretory response [24].
• Platelet-activating factor exerts mitogenic activity and stimulates expression of interleukin 6 and interleukin 8 in human lung fibroblasts via binding to its functional receptor [25].
• Extravasation and interstitial tissue migration of PMNs was induced in the rat mesentery by chemotactic stimulation with platelet-activating factor (PAF; 10(-7) M) [26].
• Platelet-activating factor (PAF-acether), an inflammatory mediator with a wide range of biological activities including neutrophil aggregation and chemotaxis, was studied for its effect on human eosinophil locomotion (chemotaxis and chemokinesis) [18].

Associations of PAF acether with other chemical compounds

• Activation of platelets by platelet-activating factor (PAF) derived from IgE-sensitized basophils. II. The role of serine proteases, cyclic nucleotides, and contractile elements in PAF-induced secretion [27].
• For maximum nonadherence, the optimum concentration was about 2 X 10(-11) M LTB4, 10(-9) M C5a des arg, 2 X 10(-8) M FMLP, 2 X 10(-9) M PAF, and 2 X 10(-8) M PMA [28].
• Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF [29].
• In addition, we studied the effect of dexamethasone on a nonpeptide inflammatory mediator, platelet-activating factor (PAF), which is not degraded by NEP or ACE [30].
• The magnitude of plasma extravasation produced by an intravenous injection of substance P (5 micrograms/kg) or PAF (10 micrograms/kg) was then assessed by using Monastral blue pigment as an intravascular tracer [30].

Gene context of PAF acether

• Surprisingly, analysis of the activation of the mitogen-activated protein (MAP) kinases p44(ERK1) and p42(ERK2), showed that ERK2, but not ERK1, was transiently activated in human eosinophils after stimulation with IL-5 or PAF [31].
• PAF synthesis was stimulated by murine and human recombinant IL 1 alpha but not by human recombinant IL 1 beta and 22K factor [32].
• Furthermore, the chemoattractants platelet-activating factor (PAF), RANTES, and C5a were also able to induce phosphotyrosine-associated PI3K activity [31].
• Together, these data show that maximal P-selectin translocation and subsequent neutrophil adhesion was mediated by VEGF-A(165) on the activation of VEGFR-2/NRP-1 complex and required PAF synthesis [33].
• Elevated numbers of adherent and emigrated leukocytes were observed in venules of LDLr-/- (compared with wild-type) mice on HCD, both under baseline conditions and after exposure to either LTB4, PAF, or TNF-alpha [34].

Analytical, diagnostic and therapeutic context of PAF acether

• METHODS AND RESULTS: Incubation of human whole blood with platelet-activating factor (PAF, 1 mumol/L) evoked downregulation of L-selectin and upregulation of CD11/CD18 adhesion receptors on neutrophils as measured by flow cytometry [35].
• Platelet-activating factor, after treatment with phospholipase A2, becomes chemotactic for monocytes, whereas the intact factor is not [36].
• In summary, this report provides the first evidence for communication between an inflammatory mediator and adhesion receptors at a molecular level, through selectin receptor ligation allowing permissive SOCE to occur following PAF stimulation of human neutrophils [37].
• Analysis of localization of GAS6 by confocal microscopy and cytofluorimetric analysis showed that it is concentrated along the plasma membrane in resting EC and treatment with PAF induces depletion and/or redistribution of the molecule [38].
• Platelet-activating factor levels of livers from sham-operated rats and from animals experiencing hepatic reperfusion for less than 6 hr were very low [39].

References