Platelet-activating factor increases platelet-dependent glycoconjugate secretion from tracheal submucosal gland

1989 ◽  
Vol 257 (6) ◽  
pp. L373-L378 ◽  
Author(s):  
T. Sasaki ◽  
S. Shimura ◽  
K. Ikeda ◽  
H. Sasaki ◽  
T. Takishima
Keyword(s):  
Platelet Activating Factor ◽  
Thromboxane A2 ◽  
Submucosal Gland ◽  
Thromboxane Receptor ◽  
Significant Stimulation ◽  
Submucosal Glands ◽  
Dose Dependent Fashion ◽  
Thromboxane Receptor Antagonist ◽  
Dose Dependent ◽  
Thromboxane A2 Analogue

Using isolated glands from feline trachea, we examined the effect of platelet-activating factor (PAF) on radiolabeled glycoconjugate release and glandular contraction by measuring induced tension in the absence or presence of platelets. PAF alone did not produce any significant glandular contraction nor any significant change in glycoconjugate release from isolated glands. In the presence of purified platelets containing no plasma, PAF (10(-8) to 10(-5) M) produced significant glycoconjugate secretion in a dose-dependent fashion, but it produced no significant glandular contraction. PAF-evoked glycoconjugate secretion was time dependent, reaching a peak response of 277% of control 15-30 min after the exposure of isolated glands to 10(-5) M PAF in the presence of platelets and returning to 135% of controls at 2 h. Platelets alone did not produce any significant stimulation in glycoconjugate release. CV-3988, a known PAF antagonist, inhibited the secretory response to PAF. Methysergide, a known antagonist to receptors for 5-hydroxytryptamine, did not alter PAF-evoked glycoconjugate secretion. Both indomethacin and SQ 29,548, a thromboxane receptor antagonist, abolished the PAF-evoked glycoconjugate secretion from isolated submucosal glands. Epithiomethanothromboxane A2, a stable thromboxane A2 analogue, produced a significant increase in glycoconjugate secretion in a dose-dependent fashion. These findings indicate that PAF increases glycoconjugate release in the presence of platelets and that the increase is dependent on some aspect of platelet function, namely thromboxane generation.

Effects of Antithrombotic Drugs in a Rat Model of Aspirin-Insensitive Arterial Thrombosis

1993 ◽  
Vol 69 (05) ◽  
pp. 509-514 ◽  
Author(s):  
W A Schumacher ◽  
T E Steinbacher ◽  
C L Heran ◽  
J R Megill ◽  
S K Durham
Keyword(s):  
Arterial Thrombosis ◽  
Light And Electron Microscopy ◽  
Platelet Activating Factor ◽  
Thrombin Inhibitor ◽  
Experimental Conditions ◽  
Once Daily ◽  
Thromboxane Receptor ◽  
Vessel Patency ◽  
Electrolytic Injury ◽  
Thromboxane Receptor Antagonist

SummaryThese studies describe experimental conditions where aspirin is less effective than other antiplatelet and anticoagulant drugs in inhibiting acute arterial thrombosis. External electrolytic injury of the rat carotid artery was used to induce occlusive thrombi in 97% of vehicle-treated rats. Thrombi were revealed by light and electron microscopy to be comprised primarily of platelets enmeshed in a fibrin network. The thrombin inhibitor D-phenylalanyl-L-prolyl-L-arginyl chloromethy ketone (PPACK; 6 mg/kg, i. v.) decreased thrombus weight by 90%. Aspirin alone (1, 10 and 30 mg/kg, i. v.), dipyridamole alone (5 mg/kg i. v.) and aspirin (1 and 10 mg/kg, i. v.) in combination with dipyridamole (5 mg/kg, i. v.) did not inhibit thrombosis. The platelet-activating factor (PAF) antagonist, WEB 2086, (1 mg/kg i. v.) was also ineffective. Other drugs had intermediate activity. Thrombi were decreased 56% by the thromboxane receptor antagonist, BMS 180,291, either alone (5.8 mg/kg i.v.) or in combination with aspirin (10 mg/kg, i.v.). Heparin (900 U/kg, i.v.), warfarin (0.25 mg/kg, p.o. once daily for 3 days) and ticlopidine (200 mg/ kg, p.o. once daily for 3 days) reduced thrombus weight by 63, 73 and 43% respectively. Reductions in thrombus weight were always associated with improvements in either average blood flow or vessel patency.

Inhibition of neutrophil L-selectin shedding: a potential anti-inflammatory effect of aprotinin

Perfusion ◽  
2000 ◽  
Vol 15 (6) ◽  
pp. 495-499 ◽  
Author(s):  
George Asimakopoulos ◽  
Kenneth M Taylor ◽  
Dorian O Haskard ◽  
R Clive Landis
Keyword(s):  
Endothelial Cell ◽  
Venous Blood ◽  
Platelet Activating Factor ◽  
Surface Expression ◽  
Cell Interaction ◽  
Dose Dependent Fashion ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Inflammatory Action ◽  
Inflammatory Effect

The cardiopulmonary bypass (CPB)-related inflammatory response involves leucocyte activation and increased leucocyte-endothelial cell interaction. L-selectin is an adhesion molecule expressed on the surface of leucocytes which participates in the initial rolling step of the leucocyte-endothelial cell adhesion cascade. L-selectin is proteolytically cleaved off the surface of leucocytes when they become activated, an event that is regarded as a marker of leucocyte activation. Aprotinin is a protease inhibitor that has been used in cardiac surgery as a haemostatic agent and also exhibits certain anti-inflammatory properties. In this study, peripheral venous blood from volunteers was pre-incubated with aprotinin at 200, 800 and 1600 kallikrein inhibiting units (kiu)/ml and stimulated with the chemoattractants N-formyl-methyl-leucyl-phenylalanine (fMLP) or platelet activating factor (PAF). Surface expression of L-selectin on neutrophils was measured using a monoclonal antibody and flow cytometry. The results demonstrate that aprotinin inhibits shedding of L-selectin in a dose-dependent fashion ( p=0.0278 and 0.0005, respectively, at 800 and 1600 kiu/ml for fMLP-stimulated shedding; p=0.0017 and 0.0010, respectively, at 200 and 800 kiu/ml for PAF-stimulated shedding). This effect may be of significance with respect to the anti-inflammatory action of aprotinin in patients undergoing CPB.

Pre- and postjunctional effects of some prostanoids in human isolated vas deferens

1991 ◽  
Vol 260 (4) ◽  
pp. R792-R797 ◽  
Author(s):  
F. Holmquist ◽  
H. Hedlund ◽  
K. E. Andersson
Keyword(s):  
Vas Deferens ◽  
Thromboxane A2 ◽  
Electrical Field Stimulation ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Concentration Dependent Manner ◽  
Thromboxane A2 Receptor ◽  
Thromboxane Receptor ◽  
Thromboxane A2 Analogue

The effects of prostaglandin (PG) E1, PGE2, the thromboxane A2 analogue U-44069, and the prostacyclin derivative iloprost were studied on isometric contractions induced by norepinephrine (NE) and by electrical field stimulation of nerves in isolated preparations of the human vas deferens. The effects of these agents on the electrically induced release of 3H from preparations preincubated with [3H]NE were also investigated. PGE1 and PGE2 inhibited the electrically induced contractions concentration dependently. U-44069 augmented the contractions without affecting baseline tension, and in preparations where the contractions had been inhibited by PGE1 or PGE2, U-44069 restored the contractions almost to starting levels. The thromboxane A2-receptor antagonist BM 13505, having no effect or inhibitory effects on electrically induced contractions, abolished the stimulatory effect of U-44069. Contractions induced by exogenous NE were augmented by U-44069, whereas PGE1 and BM 13505 were without effects. The electrically induced release of 3H was inhibited by PGE1 and PGE2 in a concentration-dependent manner, whereas U-44069 and BM 13505 increased the release of 3H. Furthermore, the inhibitory effect of PGE1 on 3H release was partly counteracted by U-44069. Iloprost had no significant effect on electrically induced contractions or on 3H release. These results suggest that, in the human vas deferens, thromboxane A2 augments contractions predominantly through a postjunctional site of action, whereas PGs of the E type have a prejunctional inhibitory effect. In addition, the pre- and post-junctional effect profiles of U-44069 and BM 13505 suggest that there may be more than one thromboxane receptor.

scholarly journals Actions of Platelet-Activating Factor on Isolated Feline and Human Cerebral Arteries

1990 ◽  
Vol 10 (3) ◽  
pp. 428-431 ◽  
Author(s):  
Tore K. Uski ◽  
Peter Reinstrup
Keyword(s):  
Receptor Antagonist ◽  
Cerebral Arteries ◽  
Platelet Activating Factor ◽  
Pial Arteries ◽  
Thromboxane Receptor ◽  
Prostanoid Production ◽  
Prostaglandin F ◽  
Basilar Arteries ◽  
Thromboxane Receptor Antagonist

The effects of platelet-activating factor (PAF) were studied on isolated feline basilar arteries (BAs) and human pial arteries (PAs). PAF contracted the BAs by 67% of the contraction induced by 124 m M K+ and the PAs by 80%. The contraction in BAs was unaffected by both indomethacin and the thromboxane receptor antagonist AH23848. PAF relaxed prostaglandin F2α-contracted arteries. In BAs 10−6 M PAF reduced the contraction by 17% and in PAs by 47%. The relaxant effects in both arteries were unaffected by indomethacin. In conclusion, PAF can act both as a constrictor and as a dilator of isolated feline and human cerebral arteries. The effects are seemingly unrelated to vascular prostanoid production.

scholarly journals Involvement of thromboxane A2 in airway mucous cells in asthma-related cough

2002 ◽  
Vol 92 (2) ◽  
pp. 763-770 ◽  
Author(s):  
Anbo Xiang ◽  
Yoshiyuki Uchida ◽  
Akihiro Nomura ◽  
Hiroaki Iijima ◽  
Tohru Sakamoto ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Allergic Airway Inflammation ◽  
Thromboxane A2 ◽  
Lavage Fluid ◽  
Mucous Cells ◽  
Thromboxane Receptor ◽  
Neurokinin Receptor ◽  
Thromboxane Synthetase ◽  
Thromboxane Receptor Antagonist

The aim of this study was to elucidate the role of thromboxane A2 (TxA2) on asthma-related cough in guinea pigs. Animals were immunosensitized and repeatedly challenged with ovalbumin as an antigen. Coughs were induced by the inhalation of 10−5 M capsaicin solution for 10 min. Thromboxane synthetase (TxS) inhibitor OKY-046 and thromboxane-receptor antagonist AA-2414 significantly inhibited cough responses in repeatedly challenged animals. Inhalation of TxA2 mimic STA-2- potentiated cough responses in normal and immunosensitized animals but not in repeatedly challenged ones. Moreover, STA-2-potentiated coughs were inhibited by administration of neurokinin-receptor antagonist FK-224. In repeatedly challenged animals, concentration of TxB2 in airway lavage fluid, expression of TxS mRNA in tracheal epithelia, and the immunostaining intensity against TxS in mucous cells of the epithelium significantly increased compared with normal and sensitized animals. These results suggest that TxA2 derived from mucous cells potentiated cough responses to capsaicin in allergic airway inflammation.

scholarly journals Effect of Platelet-activating Factor onin vitroandin vivoInterleukin-6 Production

1994 ◽  
Vol 3 (4) ◽  
pp. 281-285 ◽  
Author(s):  
B. Pignol ◽  
T. Maisonnet ◽  
P. Guinot ◽  
J. M. Mencia-Huertac ◽  
P. Braquet
Keyword(s):  
Platelet Activating Factor ◽  
Similar Extent ◽  
Rat Serum ◽  
Mouse Fibroblasts ◽  
Dose Dependent Fashion ◽  
The One ◽  
Dose Dependent ◽  
Peak Increase

The aim of the present study was to investigate the possible effect of platelet-activating factor (PAF), by comparison with interleukin-1β and polyriboinositic/polyribocytidylic (poly I–C) acid, on IL-6 production by L 929 mouse fibroblasts. At concentrations above 1 μM PAF, the production of IL-6 by mouse fibroblasts was enhanced in a dose dependent fashion. At 5 μM PAF, the peak increase (60.1 ± 19.4 U/ml) was similar to that induced by 50 μg/ml poly I–C (60.0 ± 35.0 U/ml) and higher than the one evoked by 100 U/ml IL-1β (3.8 ± 1.8 U/ml). The increase of 11-6 activity induced by 5 μM PAF was maximal after a 22 h incubation period with L 929 cells. Lyso-PAF (5 μM) also increased IL-6 activity from fibroblasts to a similar extent compared with 5 μM PAF. In addition, the IL-6 activity induced by 5 μM PAF was still observed when the specific PAF antagonist, BN 52021 (10 μM), was added to the incubation medium of L 929 cells. The result suggests that the production of IL-6 by L 929 cells evoked by PAFin vitrois not receptor mediated. Thein vivoeffect of PAF on IL-6 production was also investigated in the rat. Two hours after intravenous injection of PAF (2 to 4 μg/kg), a dramatic increase of IL-6 activity in rat serum was observed, this effect being dose dependent. The increase of IL-6 induced by 3 μg/kg PAF was not observed when the animals were treated with the PAF antagonist, BN 52021 (1 to 60 mg/kg0. These results demonstrate that PAF modulates IL-6 production and that thein vivoeffect is receptor mediated.

Glomerular responses to platelet-activating factor in the rat: role of thromboxane A2

1989 ◽  
Vol 256 (1) ◽  
pp. F35-F43 ◽  
Author(s):  
K. F. Badr ◽  
D. K. DeBoer ◽  
K. Takahashi ◽  
R. C. Harris ◽  
A. Fogo ◽  
...  
Keyword(s):  
Flow Rate ◽  
Plasma Flow ◽  
Renal Plasma Flow ◽  
Platelet Activating Factor ◽  
Thromboxane A2 ◽  
Wistar Rat ◽  
Cyclooxygenase Inhibitors ◽  
Dependent Manner ◽  
Glomerular Injury ◽  
Dose Dependent

In view of its role as a pro-inflammatory mediator in glomerular injury, we investigated the renal cortical microcirculatory responses to the intrarenal arterial administration of platelet-activating factor (PAF) in the anesthetized euvolemic Munich-Wistar rat. Close arterial administration of PAF led to dose-dependent reductions in renal plasma flow rate (RPF), glomerular filtration rate (GFR), and filtration fraction (FF), in the absence of hypotension or hemoconcentration. Single-nephron (SN) plasma flow rate (QA), SNGFR and SNFF also fell [126 +/- 7 to 101 +/- 6 nl/min (P less than 0.005), 40.6 +/- 2.1 to 21.5 +/- 2.5 nl/min (P less than 0.005), and 0.33 +/- 0.03 to 0.21 +/- 0.03 (P less than 0.025)]. PAF increased pre- and postglomerular arteriolar resistances [2.32 +/- 0.14 to 2.73 +/- 0.19 (P less than 0.005) and 1.32 +/- 0.13 to 1.45 +/- 0.10(10)dyn.s.cm-5 (P less than 0.05)]. PAF infusion also led to a dramatic reduction in the mean value for the glomerular capillary ultrafiltration coefficient, Kf [0.058 +/- 0.012 to 0.020 +/- 0.003 nl.s-1.mmHg (P less than 0.025)]. PAF-induced changes in renal hemodynamics were abolished in the presence of the cyclooxygenase inhibitors, indomethacin and ibuprofen. When administered concomitantly with a thromboxane A2 (TxA2) receptor antagonist, PAF led to significant increases in RPF and GFR. In isolated glomeruli, PAF stimulated the biosynthesis of TxB2 in a dose-dependent manner. Thus PAF depresses rat glomerular function by inducing contraction of arteriolar and mesangial smooth muscle. These effects are likely mediated via the secondary release of TxA2.

scholarly journals Differential glycosylation of alpha-1-acid glycoprotein (AGP-1) contributes to its functional diversity

2020 ◽  
Author(s):  
Mosale Seetharam Sumanth ◽  
Shancy P Jacob ◽  
Kandahalli Venkataranganayaka Abhilasha ◽  
Bhanu Kanth Manne ◽  
Venkatesha Basrur ◽  
...  
Keyword(s):  
Acute Phase ◽  
Platelet Reactivity ◽  
Platelet Activating Factor ◽  
Human Platelets ◽  
Peptide Sequence ◽  
Human Neutrophils ◽  
Intracellular Camp ◽  
Acid Glycoprotein ◽  
Dose Dependent Fashion ◽  
Dose Dependent

AbstractAlpha-1-acid glycoprotein (AGP-1) is a positive acute phase glycoprotein with uncertain functions. Serum AGP-1 (sAGP-1) is primarily derived from hepatocytes and circulates as 12 to 20 different glycoforms. We isolated a glycoform secreted from stimulated human neutrophils (nAGP-1). Its peptide sequence was identical to hepatocyte-derived sAGP-1, but nAGP-1 differed from sAGP-1 in its chromatographic behaviour, electrophoretic mobility, and glycosylation. The function of these two glycoforms also differed. sAGP-1 activated neutrophil adhesion, migration and NETosis in a dose-dependent fashion, while nAGP-1 was ineffective as an agonist for these events. Furthermore, sAGP-1, but not nAGP-1, inhibited LPS-stimulated NETosis. However, nAGP-1 inhibited sAGP-1-stimulated neutrophil NETosis. The discordant effect of the differentially glycosylated AGP-1 glycoforms was also observed in platelets where neither of the AGP-1 glycoforms alone stimulated aggregation of washed human platelets, but sAGP-1, and not nAGP-1, inhibited aggregation induced by Platelet-activating Factor (PAF) or ADP, but not by thrombin. These functional effects of sAGP-1 correlated with intracellular cAMP accumulation and were accompanied by phosphorylation of the PKA substrate Vasodialator stimulated phosphoprotein (VASP) and reduction of Akt, ERK, and p38 phosphorylation. Thus, the sAGP-1 glycoform limits platelet reactivity while nAGP-1 glycoform also limits pro-inflammatory actions of sAGP-1. These studies identify new functions for this acute phase glycoprotein and demonstrate that the glycosylation of AGP-1 controls its effects on two critical cells of acute inflammation.

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