Platelet-Activating Factor Biosynthesis in Rat Vascular Smooth Muscle Cells

Tomlinson, Paul R.; Croft, Kevin D.; Harris, Trudi; Stewart, Alastair G.

doi:10.1159/000159040

Cited by 20 publications

(7 citation statements)

References 17 publications

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“…In the previous experiments, PAF was shown to be largely retained within the cell in the first few hours following stimulation. Considering the time delay in our experiment after TNFα stimulation, the present study suggests that either smooth muscle cells in tracheal rings interact with cells expressing PAF at their surface or synthesize PAF themselves [27]. The present experiment does not permit us to specify the cellular source of PAF synthesis.…”

Section: Discussionmentioning

confidence: 63%

Tumour necrosis factor-alpha induces hyperreactivity in tracheal smooth muscle of the guinea-pig in vitro

Pennings¹,

Krämer²,

Bast³

et al. 1998

Eur Respir J

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Recent studies have implicated a role for tumour necrosis factor-alpha (TNFalpha) in the development of the asthmatic reaction. In this study, we examined the influence of TNFalpha on isotonic contraction of tracheal smooth muscle of the guinea-pig in vitro in response to methacholine. Tracheal rings were incubated with recombinant human (rh)TNFalpha (3x10(-11) M) for 30 min, and concentration-response curves to methacholine before and after incubation with rhTNFalpha were compared with the control. The present study demonstrates that rhTNFalpha increases maximal isotonic contraction of tracheal smooth muscle to methacholine (mean+/-SEM 169.6+/-43%, p<0.005). This effect was observed only after a 30 min delay between incubation and methacholine challenge testing. Experiments with 10(-13) - 10(-10) M rhTNF-alpha yielded similar results at all concentrations used. The effects of rhTNFalpha (10(-11) M) on tracheal hyperreactivity could be completely inhibited by coincubation with dimeric rTNF-receptor-p80 construct (10(-10) M) (p<0.01). In order to analyse secondary mediator release, experiments using coincubation with indomethacin (10(-5) M) and WEB 2086 (10(-6) M), a specific platelet activating factor (PAF) antagonist, demonstrated that the effect of rhTNFalpha on tracheal rings was mediated by PAF, since WEB 2086 completely inhibited rhTNFalpha-induced hyperreactivity (p<0.05). In conclusion, this study demonstrates that recombinant human tumour necrosis factor-alpha induces hyperreactivity in tracheal smooth muscle in vitro, which was shown to be mediated by platelet activating factor. Our study emphasizes the role of tumour necrosis factor-alpha in the pathophysiology of bronchial hyperresponsiveness.

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Section: Discussionmentioning

confidence: 63%

Tumour necrosis factor-alpha induces hyperreactivity in tracheal smooth muscle of the guinea-pig in vitro

Pennings¹,

Krämer²,

Bast³

et al. 1998

Eur Respir J

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“…Several enzymes are known to be regulated by G-proteins, e.g., phospholipase C, adenylate cyclase and PLA2. 53 We found previously that treatment of Kupffer cells with pertussis toxin resulted in an inhibition of ET-3-induced phospholipase C activation; in contrast, cholera toxin treatment caused potentiation of ET-3 -stimulated phospholipase C activity. These findings indicated that the effects of bacterial toxins on ET-3-induced phosphoinositide metabolism were not mediated by CAMP.…”

Section: Discussionmentioning

confidence: 80%

“…To our knowledge, there is currently only one other report of ET-induced cellular PAF synthesis. 53 This group reported that ET-1 elicited an increase in the level of PAF from extracts of cultured rat vascular smooth muscle cells.…”

Section: Discussionmentioning

confidence: 99%

Endothelin stimulates platelet-activating factor synthesis by cultured rat Kupffer cells

Mustafa¹,

Gandhi²,

Harvey³

et al. 1995

Hepatology

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Endothelins are potent peptide mediators that elicit glycogenolytic and vasoconstrictor actions in the liver. Endothelins were found to stimulate the synthesis and release of the lipid mediator platelet-activating factor in cultured rat Kupffer cells. Endothelin-mediated synthesis of platelet-activating factor required extracellular calcium in that the calcium chelator, EGTA and nifedipine, a calcium ion channel blocker, inhibited platelet-activating factor synthesis. The phospholipase A2 inhibitor, 4-bromophenacyl bromide, strongly inhibited endothelin-induced platelet activating factor synthesis. Endothelin-stimulated platelet activating factor synthesis was inhibited after treatment of Kupffer cells with cholera toxin, whereas pertussis toxin inhibited only this response to endothelin-1. Agents that elevate intracellular cyclic AMP levels were found to inhibit endothelin-induced platelet-activating factor synthesis in Kupffer cells. Staurosporine, a protein kinase C inhibitor minimized endothelin-induced platelet-activating factor synthesis but phorbol myristate acetate, an activator of protein kinase C, did not affect endothelin-induced platelet activating factor synthesis. Thus, the current study demonstrates that activation of an endothelin receptor in cultured rat Kupffer cells results in the synthesis and release of platelet-activating factor. The importance of endothelin-mediated platelet-activating factor synthesis relates to the mechanism of intercellular signaling occurring between endothelial cells (i.e., the site of endothelin synthesis) and Kupffer cells (i.e., the site of formation of secondary mediators such as platelet-activating factor and eicosanoids) within the rat liver exposed to various types of pathophysiological episodes.

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“…Previous reports have shown that smooth muscle cells of systemic [23] and pulmonary vascular origin [20] synthesize PAF following an appropriate stimulus. In this study, we show that albuterol isomers stimulate PAF production by HBSMCs in culture.…”

Section: Discussionmentioning

confidence: 99%

Albuterol Isomers Modulate Platelet-Activating Factor Synthesis and Receptor Signaling in Human Bronchial Smooth Muscle Cells

Bae

Arteaga

Raj³

et al. 2011

Int Arch Allergy Immunol

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Background: Racemic albuterol is a 50:50 mixture of the (R)- and (S)-enantiomers of albuterol. Its clinical efficacy resides in the (R)-enantiomer (levalbuterol). Studies have shown that (S)-albuterol induces human bronchial smooth muscle cell (HBSMC) proliferation via a pathway linked to platelet-activating factor (PAF), but the underlying mechanism by which (S)-albuterol augments PAF effects is not clear. In this study, we compared effect of levalbuterol and (S)-albuterol on PAF receptor (PAFr)-mediated signaling and PAF metabolism by HBSMCs after incubation with the albuterol isomers. Methods: PAF binding and inositol phosphate (IP₃) release were studied on adherent cultured cells. PAFr protein expression was measured by Western blotting, PAF synthesis and catabolism were measured in membrane and cytosolic proteins of cells incubated with albuterol isomers. Results: Compared to control conditions, (S)-albuterol increased PAF binding by 70% after 30 min of preincubation and by 150% after 24 h of preincubation. Levalbuterol had no effect on PAF binding under both conditions. (S)-albuterol also augmented PAF stimulation of IP₃ release, while levalbuterol and the racemic mixture had no effect. WEB 2170, a PAFr antagonist, inhibited the ability of (S)-albuterol to increase PAF binding or stimulate IP₃ release. (S)-albuterol stimulated PAFr protein expression. With PAF metabolism, (S)-albuterol treatment augmented PAF synthesis, but significantly inhibited PAF catabolism. Conclusions: Our data suggest that one mechanism by which (S)-albuterol stimulates HBSMC proliferation involves upregulation of PAFr-mediated effects including increased PAF synthesis and decreased PAF catabolism.

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Platelet-Activating Factor Biosynthesis in Rat Vascular Smooth Muscle Cells

Cited by 20 publications

References 17 publications

Tumour necrosis factor-alpha induces hyperreactivity in tracheal smooth muscle of the guinea-pig in vitro

Tumour necrosis factor-alpha induces hyperreactivity in tracheal smooth muscle of the guinea-pig in vitro

Endothelin stimulates platelet-activating factor synthesis by cultured rat Kupffer cells

Albuterol Isomers Modulate Platelet-Activating Factor Synthesis and Receptor Signaling in Human Bronchial Smooth Muscle Cells

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