scholarly journals Identification of platelet-activating factor as the inflammatory lipid mediator in CCl4-metabolizing rat liver

2001 ◽  
Vol 42 (4) ◽  
pp. 587-596
Author(s):  
Gopal K. Marathe ◽  
Kathleen A. Harrison ◽  
L. Jackson Roberts ◽  
Jason D. Morrow ◽  
Robert C. Murphy ◽  
...  
Keyword(s):  
Rat Liver ◽  
Platelet Activating Factor ◽  
Lipid Mediator

scholarly journals Consumption of Enriched Yogurt with PAF Inhibitors from Olive Pomace Affects the Major Enzymes of PAF Metabolism: A Randomized, Double Blind, Three Arm Trial

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 801
Author(s):  
Maria Detopoulou ◽  
Agathi Ntzouvani ◽  
Filio Petsini ◽  
Labrini Gavriil ◽  
Εlizabeth Fragopoulou ◽  
...  
Keyword(s):  
Platelet Activating Factor ◽  
Lipid Mediator ◽  
Olive Pomace ◽  
Double Blind ◽  
Promising Alternative ◽  
Catabolic Enzymes ◽  
Platelet Activating Factor Acetylhydrolase ◽  
The Impact ◽  
By Products ◽  
Apparently Healthy

Platelet-activating factor (PAF), a proinflammatory lipid mediator, plays a crucial role in the formation of the atherosclerotic plaque. Therefore, the inhibition of endothelium inflammation by nutraceuticals, such as PAF inhibitors, is a promising alternative for preventing cardiovascular diseases. The aim of the present study was to evaluate the impact of a new functional yogurt enriched with PAF inhibitors of natural origin from olive oil by-products on PAF metabolism. Ninety-two apparently healthy, but mainly overweight volunteers (35–65 years) were randomly allocated into three groups by block-randomization. The activities of PAF’s biosynthetic and catabolic enzymes were measured, specifically two isoforms of acetyl-CoA:lyso-PAF acetyltransferase (LPCATs), cytidine 5′-diphospho-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT) and two isoforms of platelet activating factor acetylhydrolase in leucocytes (PAF-AH) and plasma (lipoprotein associated phospholipase-A2, LpPLA2). The intake of the enriched yogurt resulted in reduced PAF-CPT and LpPLA2 activities. No difference was observed in the activities of the two isoforms of lyso PAF-AT. In conclusion, intake of yogurt enriched in PAF inhibitors could favorably modulate PAF biosynthetic and catabolic pathways.

Molecular determinants of lipid mediator-induced leukocyte adherence and emigration in rat mesenteric venules

1994 ◽  
Vol 266 (3) ◽  
pp. H847-H853 ◽  
Author(s):  
B. J. Zimmerman ◽  
J. W. Holt ◽  
J. C. Paulson ◽  
D. C. Anderson ◽  
M. Miyasaka ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Platelet Activating Factor ◽  
Leukotriene B4 ◽  
Intercellular Adhesion Molecule ◽  
Lipid Mediator ◽  
Leukocyte Rolling ◽  
Leukocyte Adherence ◽  
Intercellular Adhesion Molecule 1 ◽  
Rolling Velocity ◽  
Molecular Determinants

The objective of this study was to identify the molecular determinants of leukocyte rolling, adherence, and emigration elicited in postcapillary venules by the lipid mediators leukotriene B4 (LTB4) or platelet-activating factor (PAF). Leukocyte-endothelial cell adhesion and shear rate were monitored in rat mesenteric venules during superfusion with either LTB4 or PAF in the presence or absence of monoclonal antibodies (MAbs) directed against either leukocyte (CD18, CD11b) or endothelial cell [intercellular adhesion molecule 1 (ICAM-1), E-selectin, P-selectin] adhesion glycoproteins. In untreated animals and in animals receiving a nonbinding control MAb, LTB4 and PAF increased the number of both adherent (8- and 4-fold, respectively) and emigrated (14- and 8-fold, respectively) leukocytes, while reducing leukocyte rolling velocity (36 and 33%, respectively). The LTB4- and PAF-induced leukocyte adherence and emigration were significantly attenuated by pretreatment with MAbs directed against CD18, CD11b, ICAM-1, and E-selectin, but not P-selectin. The reduction in leukocyte rolling velocity induced by LTB4 was not affected by any of the MAbs; however, both P- and E-selectin MAbs significantly attenuated the reduction in leukocyte rolling velocity elicited by PAF. The results of this study indicate that the leukocyte adherence and emigration induced by both LTB4 and PAF are mediated by CD11b/CD18 on leukocytes and by ICAM-1 and E-selectin on endothelial cells. The molecular determinant of leukocyte rolling appears to be mediator specific, with the selectins mediating the rolling elicited by PAF.

scholarly journals Platelet-activating Factor, a Molecular Sensor for Cellular Damage, Activates Systemic Immune Suppression

2002 ◽  
Vol 195 (2) ◽  
pp. 171-179 ◽  
Author(s):  
Jeffrey P. Walterscheid ◽  
Stephen E. Ullrich ◽  
Dat X. Nghiem
Keyword(s):  
Skin Cancer ◽  
Uv Radiation ◽  
Immune Suppression ◽  
Critical Role ◽  
Platelet Activating Factor ◽  
Cellular Damage ◽  
Uv Exposure ◽  
Delayed Type Hypersensitivity ◽  
Lipid Mediator ◽  
Paf Receptor

Ultraviolet (UV) radiation plays a critical role in the induction of nonmelanoma skin cancer. UV radiation is also immune suppressive, and the immune suppression induced by UV irradiation has been identified as a major risk factor for skin cancer induction. Previously, we showed that UV exposure activates a cytokine cascade involving prostaglandin (PG)E2, interleukin (IL)-4, and IL-10 that induces immune suppression. However, the earliest molecular events that occur immediately after UV exposure, especially those upstream of PGE2, are not well defined. UV-irradiated keratinocytes secrete the inflammatory phospholipid mediator, platelet-activating factor (PAF). Because PAF upregulates the production of immunomodulatory compounds, including PGE2, we tested the hypothesis that UV-induced PAF activates cytokine production and initiates UV-induced immune suppression. Both UV and PAF activated cyclooxygenase (COX)-2 and IL-10 reporter gene construct transcription. PAF mimicked the effects of UV in vivo and suppressed delayed-type hypersensitivity (DTH). Furthermore, immune suppression was blocked when UV-irradiated mice were injected with PAF receptor antagonists. In addition to the well-known role of PAF as a proinflammatory lipid mediator, we propose that the PAF receptor senses cellular damage through the recognition of PAF and/or PAF-like molecules, such as oxidized phosphatidylcholine, which activates cytokine transcription and induces systemic immune suppression.

Circulatory effects of PAF-acether in newborn piglets

1989 ◽  
Vol 256 (1) ◽  
pp. H205-H212 ◽  
Author(s):  
L. M. Bradley ◽  
R. E. Goldstein ◽  
G. Feuerstein ◽  
J. F. Czaja
Keyword(s):  
Cardiac Index ◽  
Platelet Activating Factor ◽  
Resistance Index ◽  
Receptor Blocker ◽  
Lipid Mediator ◽  
Inhibitory Influence ◽  
Newborn Piglets ◽  
Inflammatory Conditions ◽  
Circulatory Effects ◽  
Potent Vasoconstrictor

Platelet-activating factor (PAF-acether) is a lipid mediator that can exhibit potent vasoconstrictor influence in the pulmonary vessels. Therefore, the release of PAF-acether during inflammatory conditions in newborns might cause deleterious increases in pulmonary vascular tone. Thirty-four anesthetized open-chest newborn piglets were given 0.01-1 nmol PAF-acether iv. In separate experiments, animals were untreated or treated with either indomethacin (a cyclooxygenase inhibitor), SQ 29548 (a thromboxane receptor blocker), or LY 171883 (a leukotriene receptor blocker). The primary hemodynamic change was a 67 to 1,537% increase in the pulmonary vascular resistance index (PVRI) (P less than 0.01): mean pulmonary artery pressure (PAP) rose significantly at all doses tested, whereas only the largest dose consistently decreased cardiac index. Treatment with indomethacin or SQ 29548 prevented the decrease in cardiac index and attenuated the PAF-acether-induced rises in PAP and PVRI. Vehicle and LY 171883 had no effect. The inhibitory influence of indomethacin and SQ 29548 suggests that an important component of PAF-acether's pulmonary vasoconstrictor action is mediated (at least in the newborn piglet) by cyclooxygenase products, most likely thromboxane.

scholarly journals Down-regulation of LPCAT expression increases platelet-activating factor level in cirrhotic rat liver: Potential antiinflammatory effect of silybin

2013 ◽  
Vol 1832 (12) ◽  
pp. 2019-2026 ◽  
Author(s):  
Eleonora Stanca ◽  
Gaetano Serviddio ◽  
Francesco Bellanti ◽  
Gianluigi Vendemiale ◽  
Luisa Siculella ◽  
...  
Keyword(s):  
Rat Liver ◽  
Platelet Activating Factor ◽  
Antiinflammatory Effect ◽  
Factor Level ◽  
Down Regulation

scholarly journals Multiprong control of glioblastoma multiforme invasiveness: blockade of pro-inflammatory signaling, anti-angiogenesis, and homeostasis restoration

2021 ◽  
Author(s):  
Nicolas G. Bazan ◽  
Madigan M. Reid ◽  
Valerie A. Cruz Flores ◽  
Juan E. Gallo ◽  
William Lewis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Glioblastoma Multiforme ◽  
Platelet Activating Factor ◽  
Angiogenesis Inhibitor ◽  
Standard Of Care ◽  
Lipid Mediator ◽  
Glial Tumor ◽  
Poor Overall Survival ◽  
Adaptive Mutations ◽  
Novel Host

AbstractGlioblastoma multiforme (GBM) is the most invasive type of glial tumor with poor overall survival, despite advances in surgical resection, chemotherapy, and radiation. One of the main challenges in treating GBM is related to the tumor’s location, complex and heterogeneous biology, and high invasiveness. To meet the demand for oxygen and nutrients, growing tumors induce new blood vessels growth. Antibodies directed against vascular endothelial growth factor (VEGF), which promotes angiogenesis, have been developed to limit tumor growth. Bevacizumab (Avastin), an anti-VEGF monoclonal antibody, is the first approved angiogenesis inhibitor with therapeutic promise. However, it has limited efficacy, likely due to adaptive mutations in GBM, leading to overall survival compared to the standard of care in GBM patients. Molecular connections between angiogenesis, inflammation, oxidative stress pathways, and the development of gliomas have been recognized. Improvement in treatment outcomes for patients with GBM requires a multifaceted approach due to the converging dysregulation of signaling pathways. While most GBM clinical trials focus on “anti-angiogenic” modalities, stimulating inflammation resolution is a novel host-centric therapeutic avenue. The selective therapeutic possibilities for targeting the tumor microenvironment, specifically angiogenic and inflammatory pathways expand. So, a combination of agents aiming to interfere with several mechanisms might be beneficial to improve outcomes. Our approach might also be combined with other therapies to enhance sustained effectiveness. Here, we discuss Suramab (anti-angiogenic), LAU-0901 (a platelet-activating factor receptor antagonist), Elovanoid (ELV; a novel lipid mediator), and their combination as potential alternatives to contain GBM growth and invasiveness.

79 THE CELL-CYCLE RELATED NUCLEAR LOCALIZATION OF PLATELET-ACTIVATING FACTOR IN BOVINE AND MURINE EMBRYO DEVELOPMENT

2017 ◽  
Vol 29 (1) ◽  
pp. 147
Author(s):  
L. T. M. Vandenberghe ◽  
C. De Schauwer ◽  
B. Heindryckx ◽  
A. Van Soom
Keyword(s):  
Cell Cycle ◽  
Embryo Development ◽  
Intracellular Localization ◽  
Recovery Period ◽  
Platelet Activating Factor ◽  
Molecular Probes ◽  
Primary Antibody ◽  
Immunofluorescent Staining ◽  
Lipid Mediator ◽  
Murine Embryos

Platelet-activating factor (PAF) is a lipid mediator produced by a wide variety of cells and well known for its involvement in host defense and platelet aggregation. In embryo development, PAF functions as an embryotropin and a marker of embryo quality and viability in human and mice. However, only limited information is available concerning its function during in vitro culture of bovine embryos. Bovine and murine embryos were collected at different time points according to their development (4–8-16 cells-morula-blastocyst; 8–10 embryos per replicate; 4 replicates). Phospholipid expression and intracellular localization was evaluated by immunofluorescent staining and confocal scanning microscopy. In short, the zona pellucida of the embryos was removed using 0.5% protease (from Streptomyces griseus). After a recovery period of 30 min, embryos were fixed in 4% paraformaldehyde and permeabilized (0.5% Triton X-100 and 0.05% Tween20) overnight at 4°C. Subsequently, embryos were transferred to blocking solution (30% goat serum and 0.05% Tween20) overnight at 4°C to block nonspecific binding sites. Next, embryos were incubated overnight with primary antibody against PAF (1:100; Emelca Bioscience, Breda, the Netherlands) at 4°C, followed by 1 h of incubation with secondary goat anti-rabbit (Alexa Fluor 488; 1:500; Abcam, Cambridge, MA, USA). Nuclei were visualised by 20 min incubation with Hoechst 33342 (1:500, Molecular Probes) in the dark. As a negative control, the primary antibody was replaced with rabbit IgG whole molecule (Rockland Immunochemicals, Limerick, PA, USA). Using specific lipid antibodies, we were able to show that PAF accumulates in the nuclei of pre-implantation bovine and murine embryos. Suprisingly, the localization correlated with the cell cycle: a clear nuclear signal was observed during interphase and a redistribution to the cytoplasm happened upon nuclear envelope breakdown at mitosis. To confirm this finding, bovine blastocysts (10 embryos per replicate, 3 replicates) were incubated for 12 h with the microtubule destabilising agent nocodazole (2 μM; Sigma, Germany). Embryos were analysed using immunofluorescent staining as described above. Nocodazole treatment resulted in arrest of at least 20% of the embryonic cells at mitosis. Upon treatment, we were able to reproduce the cell-cycle dependent shuttling between M-phase and interphase nuclei of PAF. We are the first to attribute this unique feature of nucleo-cytoplasmic redistribution to an important embryonic growth factor such as PAF. Further research will be needed to unravel the exact pathway and function of PAF in the nucleus and its implications on embryonic development.

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