Disease relevance of PAF acether

• The data indicate that TNF induces neutrophil-dependent pulmonary edema associated with increased Ppc (mediated by TXA2 and PAF), increased Kf,c (mediated by PAF), and changes in endothelial peripheral actin bands [1].
• Thus, it appears that TNF release alone, without a sufficient increase in PAF, is incapable of causing severe hypotension [2].
• In man, inhalation of PAF causes a bronchospasm and induces a bronchial hyperreactivity [3].
• Among the mediators involved in the pathophysiologic mechanisms that underly the reactions of the acute and delayed phases of bronchospasm induced by allergens in man, platelet-activating factor (PAF) could play an important role, in particular by its effects on platelets [3].
• In addition, Langendorff-perfused PI3Kgamma-null hearts showed a better contractile recovery after ischemia/reperfusion, a condition where PAF is known to be an important player in depressing contractility [4].

High impact information on PAF acether

• These results demonstrate that oral allergen-induced diarrhea associated with experimental Th2 intestinal inflammation is largely mast cell, IgE, serotonin, and PAF dependent [5].
• We demonstrated that human endothelial cells synthesize two vasoactive lipids, platelet-activating factor (PAF) and prostacyclin, in response to alpha toxin treatment [6].
• Similar results were observed in neutrophils activated with platelet-activating factor (PAF) [7].
• Hly provoked rapid secretion of elastase and myeloperoxidase, generation of superoxide, and synthesis of platelet-activating factor (PAF) and lyso-PAF [8].
• E-selectin permits communication between PAF receptors and TRPC channels in human neutrophils [9].

Chemical compound and disease context of PAF acether

• Pretreatment of the animal with PAF antagonist, SRI 63-441, markedly ameliorated the hypotension and tissue injury [2].
• Circulating levels of platelet-activating factor (PAF) are high in the fetus, and PAF is active in maintaining high PVR in fetal hypoxia (Ibe BO, Hibler S, Raj J [10].
• Platelet-activating factor (PAF) is an inflammatory mediator capable of inducing protracted inflammation of the airways and bronchial hyperreactivity [11].
• Control of local blood flow in pulmonary inflammation: role for neutrophils, PAF, and thromboxane [12].
• No increase in plasma histamine during PAF-induced airway obstruction in allergic asthmatics [13].

Biological context of PAF acether

• Whereas 80% of binding sites exposed by PAF closed within 30 minutes (22 degrees C), alpha-thrombin (0.1 U/mL) triggered long-lasting exposure of binding sites for [125I]-fibrinogen and [125I]-fibronectin [14].
• Studies using WEB-2086 (37 microM), a platelet activating factor (PAF) receptor antagonist, indicated that PAF mediated the increased vascular permeability (Kf,c, 0.107 +/- 0.014 g/min/cm H2O/g at 30 minutes using WEB-2086) and, in part, the increased Ppc (Ppc, 8.4 +/- 0.7 cm H2O at 60 minutes using WEB-2086) [1].
• We further report that incubation of neutrophils with TNFalpha results in the p38 MAPK-dependent phosphorylation of a subpopulation of p47(phox) and p67(phox) molecules, whereas PAF priming results in phosphorylation only of p67(phox) [15].
• In animals, inhalation or injection of PAF causes a platelet-dependent bronchoconstriction that is blocked by prior administration of an antiplatelet antiserum and accompanied by platelet accumulation in the pulmonary vessels [3].
• There was no difference between platelet counts, plasma concentrations of platelet factor 4 and beta-thromboglobulin, and platelet aggregation induced by several agonists (adrenaline, arachidonic acid, or PAF) before and immediately after the allergen bronchial provocation test [3].

Anatomical context of PAF acether

• Here, the biological activities and the activation profile of Eotaxin were further characterized and compared with those of other eosinophil chemotaxins such as complement fragment C5a (C5a), platelet-activating factor (PAF), and RANTES in human eosinophils [16].
• In this study, we determined which mediator from cutaneous mast cells mediates substance P-induced granulocyte infiltration in the skin by the use of two mediator antagonists; one for platelet activating factor (PAF) CV-6209 and the other for leukotriene B4 (LTB4) ONO-4057 [17].
• We assessed the adrenergic-receptor system in individuals with bronchial hyperreactivity, beta-Adrenergic receptors on mononuclear cell membranes, alpha-adrenergic receptors on platelet membranes, and the cAMP response in these cell types to different stimuli, including platelet-activating factor (PAF), were determined [18].
• The levels of L-myo-[3H]inositol 1,4,5,6-tetrakisphosphate in primary-cultured macrophages are not acutely sensitive to PAF [19].
• The migration of anti-CD18 mAb-treated PMNLs was not inhibited by function-blocking mAbs to sialyl Lewisx, L-selectin, beta 1 or alpha 4 integrin, the beta 3-related leukocyte response integrin, IL-8, or platelet-activating factor (PAF) antagonists, alone or in combination [20].

Associations of PAF acether with other chemical compounds

• Previous studies have shown that binding sites for fibrinogen on platelets stimulated with platelet-activating factor (PAF), adenosine diphosphate or epinephrine rapidly close in the absence of fibrinogen [14].
• Similar to PAF, alpha-thrombin-exposed sites rapidly closed after addition of the protein kinase C inhibitor staurosporine (1 mumol/L) or dibutyryl cyclic adenosine monophosphate (250 mumol/L) [14].
• In contrast, the PAF antagonist inhibited Ag-induced eosinophil infiltration of mouse skin, whereas the LTB4 antagonist inhibited the Ag-induced neutrophil infiltration [17].
• However, pretreatment with the PAF antagonist affected neither substance P-induced neutrophil nor eosinophil infiltration at 6 h [17].
• The mathematic analysis of the effects of ciprofloxacin showed that time to maximal activity was between 10.4 hours (PAF-dependent [Ca2+]i increase), and 15 hours (fMLP-induced superoxide anion and chemiluminescence production) [21].

Gene context of PAF acether

• VEGF-mediated endothelial P-selectin translocation: role of VEGF receptors and endogenous PAF synthesis [22].
• Collectively, fMLP stimulates ROS of neutrophil through TNF-alpha signaling; PAF stimulates that of neutrophil through both TNF-alpha-dependent and TNF-alpha-independent pathway [23].
• PAF treatment increased ROS of neutrophil in WT and Tnfrsf1a-/- mice [23].
• In contrast, PAF-induced enhancement of eosinophils binding to VCAM-1 or MAdCAM-1 was alpha 4 beta 7-dependent [24].
• At optimal concentrations the changes induced by MCP-4 were weaker than the effects after stimulation with PAF and comparable to those obtained by RANTES and Eotaxin [25].

Analytical, diagnostic and therapeutic context of PAF acether

• 3. PAF (100 nM) and fMLP (100 nM) induced activation of NF-kappaB as determined by degradation of inhibitory factor B alpha (IkappaB alpha) using Western blotting in cytosolic extracts and by binding to DNA using electrophoretic mobility shift assay (EMSA) in nuclear extracts [26].
• 4. Neither the two PAF antagonists nor ketotifen had any effect on bronchoalveolar lavage (BAL) eosinophil numbers [27].
• Infusion of PAF into the isolated perfused rat lung caused vasoconstriction [mean effective concn (EC50) = 0.88 nmol], caused bronchoconstriction (EC50 = 0.71 nmol), and increased the capillary filtration coefficient (EC50 = 1.4 nmol) [28].
• Twenty-one asthmatic children were evenly divided into three groups and each group performed a double-blind, placebo-controlled and crossover study on the effect of aerosolized BN52021, a PAF antagonist, on the bronchoconstriction induced by PAF, methacholine, or specific allergen, respectively [11].
• Standards of PAF and lyso-PAF were visualized with iodine vapors after separation by thin layer chromatography [29].

References