scholarly journals Macrophage Derived Platelet Activating Factor Implicated in the Resolution Phase of Gouty Inflammation

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Darshna Yagnik
Keyword(s):  
Human Blood ◽  
Platelet Activating Factor ◽  
Inflammatory Factors ◽  
Monosodium Urate ◽  
Resolution Analysis ◽  
Paf Receptor ◽  
Factor Secretion ◽  
Msu Crystals ◽  
Paf Receptor Antagonist

Human blood derivedin vitrodifferentiated monocytes or macrophages are a population of cells which have been investigated over the years to determine the role these cells play in the resolution phase of gout. Macrophages are able to phagocytose monosodium urate monohydrate (MSU) crystals without releasing inflammatory factors. This study analysed macrophage platelet activating factor secretion and its possible role in the pathway of gout resolution. Analysis of sunatants fromin vitrodifferentiated macrophages stimulated with MSU crystals revealed the secretion of platelet activating factor (PAF)  1.54±0.10mean ± SEM; ng/mL per 106cells. This secretion was absent in immature monocytes treated similarly. When these monocytes were pretreated with recombinant human PAF-acetylhydrolase (rhuPAF-AH) and MSU crystals resulted in TNFαsuppression. Addition of WEB2086, a platelet activating factor (PAF) antagonist, to differentiated macrophages with MSU crystals unmasked TNFαsecretion0.7±0.06mean ± SEM; ng/mL per 106cells. This study identifies a role for PAF and the PAF receptor antagonist in the pathway by which macrophages ingest MSU crystals and resolve the concomitant inflammation.

scholarly journals Neutrophil migration across monolayers of cytokine-prestimulated endothelial cells: a role for platelet-activating factor and IL-8.

1992 ◽  
Vol 117 (3) ◽  
pp. 565-572 ◽  
Author(s):  
T W Kuijpers ◽  
B C Hakkert ◽  
M H Hart ◽  
D Roos
Keyword(s):  
Endothelial Cells ◽  
Neutrophil Migration ◽  
Platelet Activating Factor ◽  
Human Neutrophils ◽  
Neutrophil Adherence ◽  
Paf Receptor ◽  
And Migration ◽  
Web 2086 ◽  
Paf Receptor Antagonist

In a previous study we observed that neutrophils respond with a rapid rise in [Ca2+]i during adherence to cytokine-activated endothelial cells (EC), caused by EC membrane-associated platelet-activating factor (PAF). In the present study, we investigated whether this form of PAF was important in neutrophil adherence and migration across monolayers of rIL-1 beta- or rTNF alpha-prestimulated EC. PAF receptor antagonists prevented neutrophil migration across cytokine-pretreated EC by approximately 60% (P less than 0.005) without interfering with the process of adherence. The antagonists WEB 2086 and L-652,731 had no effect on neutrophil migration across resting EC induced by formylmethionyl-leucyl-phenylalanine (FMLP). A murine anti-IL-8 antiserum was found to also partially inhibit the neutrophil transmigration across cytokine-activated EC. When the anti-IL-8 antiserum was used in combination with a PAF receptor antagonist, neutrophil migration across cytokine-pretreated monolayers of EC was completely prevented. During transmigration, LAM-1 and CD44 on the neutrophils were down-modulated; both WEB 2086 and anti-IL-8 antiserum partially prevented this down-modulation caused by cytokine-prestimulated EC. Our results indicate that human neutrophils are activated and guided by EC-associated PAF and EC-derived IL-8 during the in vitro diapedesis in between cytokine-stimulated EC.

Exogenous xanthine promotes neutrophil adherence to cultured endothelial cells

1997 ◽  
Vol 273 (2) ◽  
pp. G342-G347
Author(s):  
H. Ichikawa ◽  
R. E. Wolf ◽  
T. Y. Aw ◽  
N. Ohno ◽  
L. Coe ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tissue Injury ◽  
Umbilical Vein ◽  
Platelet Activating Factor ◽  
Adhesion Assay ◽  
Neutrophil Adherence ◽  
Paf Receptor ◽  
Umbilical Vein Endothelial Cells ◽  
Adhesive Effect ◽  
Paf Receptor Antagonist

Oxidants generated by endothelial xanthine oxidase (XO) can help trigger free radical-mediated tissue injury. An important event in oxidant-mediated tissue injury is neutrophil-endothelial adhesion. Although activation of endothelial XO increases adhesion, little is known about xanthine in the adhesive effect of XO. This study examined administered xanthine on the adhesion of neutrophils. Endothelial [human umbilical vein endothelial cells (HUVEC)] monolayers were exposed to xanthine (15 min), and neutrophils were allowed to adhere to HUVEC in an adhesion assay. Adhesion was dose dependently increased by xanthine (3-100 microM). Either catalase (1,000 U/ml), oxypurinol (XO inhibitor; 100 microM), or platelet-activating factor (PAF) receptor antagonist (WEB 2086; 10 microM) reduced neutrophil adhesion. Superoxide dismutase (1,000 U/ml) had no effect. Pretreatment of HUVEC with 50 microM tungsten also blocked xanthine-induced adherence. Adhesion was also inhibited by preincubation with 100 U/ml heparin. Finally, anti-P-selectin antibody (PB1.3; 20 micrograms/ml) attenuated adhesion. Our results indicate that xanthine may promote neutrophil-endothelial adhesion via a hydrogen peroxide- and PAF-mediated P-selectin expression.

Platelet-activating factor antagonism and streptokinase-induced hypotension in clinical acute myocardial infarction

2001 ◽  
Vol 100 (6) ◽  
pp. 601-607 ◽  
Author(s):  
Roger TAYLOR ◽  
Daniel FATOVICH ◽  
Thomas HITCHCOCK ◽  
Catherine MORRISON ◽  
Lloyd CURTIS
Keyword(s):  
Myocardial Infarction ◽  
Blood Pressure ◽  
Acute Myocardial Infarction ◽  
Receptor Antagonist ◽  
Platelet Activating Factor ◽  
Systolic Pressure ◽  
Induced Hypotension ◽  
Paf Receptor ◽  
Double Blinded ◽  
Paf Receptor Antagonist

Continuing efforts are being made to improve thrombolytic therapy for acute myocardial infarction (AMI). The rate of streptokinase (SK) infusion is commonly limited by the hypotension that is induced. If this could be avoided, an accelerated regimen of SK could be given, analagous to that used for other thrombolytic agents such as alteplase. The mechanism of the SK-induced hypotension is unknown, but there is some evidence that platelet-activating factor (PAF) plays a role. The potent PAF receptor antagonist lexipafant (10 mg) (n = 35), or matching placebo (n = 36), was administered intravenously over 5 min, in a randomized double-blinded protocol, to consecutive patients about to receive SK for AMI; all but three had inferior MI, because of the preference for strategies other than SK therapy in patients with anterior MI. The rate of infusion of SK was set to give 1.5×106 units over 30 min, anticipating significant hypotension. Blood pressure fell sharply over the first 10 min of SK administration. The maximum fall in systolic blood pressure occurred between 8 and 12 min, and averaged 43±28 mmHg (mean±S.D.) and 40±26 mmHg in patients given placebo and lexipafant respectively. Systolic pressure having fallen to < 90 mmHg, according to protocol the SK administration rate was reduced in 21 of 36 (58%) of patients given placebo and in 19 of 35 (54%) of patients given lexipafant. The total SK dose was given to all subjects over 40.3±17.5 and 40.2±13.4 min for the placebo and lexipafant groups respectively. Peak and time integrals of creatine kinase were not different in the two groups. There were no adverse effects attributable to lexipafant. It is concluded that the PAF receptor antagonist lexipafant has no significant effect on SK-induced hypotension and does not facilitate an accelerated regimen of administration.

scholarly journals Invasion of Human Vascular Endothelial Cells byActinobacillus actinomycetemcomitans via the Receptor for Platelet-Activating Factor

2000 ◽  
Vol 68 (9) ◽  
pp. 5416-5419 ◽  
Author(s):  
Harvey A. Schenkein ◽  
Suzanne E. Barbour ◽  
C. R. Berry ◽  
Barbara Kipps ◽  
John G. Tew
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Platelet Activating Factor ◽  
Systemic Circulation ◽  
Oral Bacteria ◽  
Periodontal Pathogen ◽  
Vascular Endothelial ◽  
Transmission Electron ◽  
Paf Receptor ◽  
Paf Receptor Antagonist

ABSTRACT Strains of the periodontal pathogen Actinobacillus actinomycetemcomitans are variable with respect to display of phosphorylcholine (PC)-bearing antigens. We have examined strains ofA. actinomycetemcomitans with and without PC to assess their ability to invade endothelial cells via the receptor for platelet-activating factor (PAF). Results of antibiotic protection assays indicate that PC-bearing A. actinomycetemcomitansinvade human vascular endothelial cells by a mechanism inhibitable by CV3988, a PAF receptor antagonist, and by PAF itself. The invasive phenotype was verified by transmission electron microscopy. A PC-deficient strain of this organism was not invasive. This property, in addition to the established ability of A. actinomycetemcomitans to invade epithelial cells, may provide this organism with access to the systemic circulation. The ability of PC-bearing oral bacteria to access the circulation may also explain the elevated levels of anti-PC antibody in serum found in patients with periodontitis.

Monosodium Urate Crystals Bind with Idiotype Protein and Promote Dendritic Cells to Induce Cytotoxic T Cells in Vitro

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4904-4904
Author(s):  
Ippei Sakamaki ◽  
Kunihiro Inai ◽  
Takanori Ueda ◽  
Hiroshi Tsutani
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cytotoxic T Cells ◽  
Target Cells ◽  
Monosodium Urate ◽  
Cd4 Cells ◽  
Antigenic Protein ◽  
Positively Charged ◽  
Msu Crystals

Abstract Monosodium urate (MSU) crystals have been studied to act as a key substance in local immunoreactions. MSU released from damaged cells works as an endogenous danger signal to antigen-presenting cells. MSU crystals evoke specific cell immunity and work as an adjuvant in a mouse model. The crystals also have another unique characteristic to bind with positively charged proteins, which could help to deliver some antigens into human dendritic cells (DCs). We focused on the application of MSU crystals as a not only an adjuvant but also as a carrier of positively charged antigenic protein to induce human cytotoxic T cells (CTLs) efficiently in vitro. We confirmed that MSU crystals facilitated human DCs to express the maturation marker, CD83, deliver (Fab′)2 attaching to the crystals. In order to determine whether MSU crystals facilitate the T-cell proliferation activity of DCs, the proliferative effects of DCs on allogeneic CD4+ cells were investigated. DCs pulsed with MSU crystals significantly facilitated the proliferation of allogeneic CD4+ cells when compared to DCs alone. The stimulation index (SI) was 2.5 ± 0.1 and 1.7 ± 0.1, respectively. When using DCs pulsed with the Fab attached to MSU crystals, the proliferation of CD4+ cells was significantly greater than when using DCs pulsed with Fab alone. The SI was 2.6 ± 0.2 and 1.9 ± 0.1, respectively. No significant differences were seen in the proliferation of allogeneic CD4+ cells between DCs pulsed with the Fab attached to MSU and DCs pulsed with MSU alone. We selected the multiple myeloma IM-9 cell line and its product idiotype (Id) protein as an ideal pair of target cells and positively charged tumor-specific antigen, respectively. After sensitizing DCs derived from HLA-A matched volunteers pulsed with tumor-specific monoclonal IgG-Fab fragments (IM-9 Fab) attached to MSU crystals, the CD8+ T cells stimulated by the DCs killed significantly more target cells (38.5 ± 3.5%, n=4) than those stimulated by DCs pulsed with IM-9 Fab alone (3.5 ± 7.5%). These cytotoxic effects of CD8+ cells stimulated by the DCs pulsed with IM-9 Fab attached to MSU crystals were reduced (3.6 ± 1.7%) when MSU crystals were pre-coated with fetal bovine serum to block to bind with IM-9 Fab. For efficient induction of CTLs, it is necessary for Id proteins to attach to MSU crystals. MSU crystals have some advantages of a protein carrier binding with positively charged proteins and delivering antigenic protein into DCs, as well as an adjuvant promoting DC maturation and inducing CTLs.

scholarly journals Receptor mechanisms of PAF mediated lymphatic constriction in the canine forelimb

1992 ◽  
Vol 1 (6) ◽  
pp. 391-395 ◽  
Author(s):  
D. E. Dobbins
Keyword(s):  
Smooth Muscle ◽  
Receptor Antagonist ◽  
Lymphatic Vessel ◽  
Perfusion Pressure ◽  
Muscle Tone ◽  
Platelet Activating Factor ◽  
Arterial Infusion ◽  
Paf Receptor ◽  
Transport Fluid ◽  
Paf Receptor Antagonist

Platelet activating factor (PAF) is a potent inflammatory lipid. In this study we assessed the ability of PAF to impact lymphatic vessel function by altering prenodal lymphatic resistance. Intralymphatic PAF (7.47 × 10−6, 7.47 × 10−5and 7.47 × 10−4M) increased lymphatic perfusion pressure at the two highest infusion rates. PAF mediated lymphatic constriction was not altered by the intra-arterial infusion of phentolamine but was blocked by the intra-arterial infusion of the PAF receptor antagonist WEB 2170. These data indicate that in addition to PAF's effects on microvascular permeability, this agent may also impact the ability of the lymphatics to transport fluid through alterations in lymphatic smooth muscle tone. PAF mediated lymphatic constriction is not mediated by α-receptors but rather through PAF receptor mediated mechanism.

Effect of platelet-activating factor (PAF) receptor antagonist (BN52021) on acetaminophen-induced acute liver injury and regeneration in rats

2005 ◽  
Vol 26 (1) ◽  
pp. 97-105 ◽  
Author(s):  
A. D. Grypioti ◽  
S. E. Theocharis ◽  
C. A. Demopoulos ◽  
Z. Papadopoulou-Daifoti ◽  
A. C. Basayiannis ◽  
...  
Keyword(s):  
Liver Injury ◽  
Receptor Antagonist ◽  
Acute Liver Injury ◽  
Platelet Activating Factor ◽  
Paf Receptor ◽  
Paf Receptor Antagonist
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