Paf

Koltai, M.; Hosford, David; Guinot, Philippe; Esanu, André; Braquet, P.

doi:10.2165/00003495-199142020-00002

Cited by 112 publications

(44 citation statements)

References 262 publications

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“…Both the hypotension and vascular hyporeactivity to noradrenaline caused by injection of LPS were attenuated by BN52021. Thus, the beneficial effect of BN52021 on the cardiovascular dysfunction elicited by LPS (i) confirms that the release of PAF elicited by LPS contributes importantly to the pathophysiology of endotoxin shock (Floch et al, 1989;Rabinovici et al, 1990;Yue et al, 1990;Sanchez Crespo & FernAndez-Gallardo, 1991;Torley et al, 1992;Ogata et al, 1993;Koltai et al, 1994) (Marcheselli et al, 1990), and that WEB2086 inhibits the actions of PAF released intracellularly in leukocytes and endothelial cells (Stewart et al, 1990). Interestingly, in many different cell types, including macrophages, neutrophils and endothelial cells, the majority of PAF is retained intracellularly upon stimulation (Lynch & Henson, 1986).…”

Section: Tnf-ca Measurementsmentioning

confidence: 76%

“…In various animal models, injection of exogenous PAF results in systemic vasodilatation and hypotension (Braquet et al, 1987;Sanchez Crespo & Fema'ndez-Gallardo, 1991;Koltai et al, 1994). Here, the early (60 min) hypotension and hyporeactivity to noradrenaline elicited by LPS are attenuated by BN52021, suggesting the extracellular release of PAF by LPS as a systemic vasodilator and mediator of the early decrease in pressor response to noradrenaline.…”

Section: Tnf-ca Measurementsmentioning

confidence: 99%

“…When given exogenously to animals, PAF mimics many of the pathophysiological features of septic shock (for reviews, see Braquet et al, 1987;Sanchez Crespo & Fernandez-Gallardo, 1991;Koltai et al, 1994). For instance, in various species, intravenous injection of PAF results in cardiovascular dysfunction, including hypotension, peripheral vasodilatation and plasma extravasation, and in multiple organ failure, such as a reduced kidney and lung function.…”

Section: Introductionmentioning

confidence: 99%

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Role for intracellular platelet‐activating factor in the circulatory failure in a model of Gram‐positive shock

Kimpe¹,

Thiemermann

Vane

1995

British J Pharmacology

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This study investigates the effects of two structurally different antagonists of platelet‐activating factor (PAF), BN52021 and WEB2086, on the circulatory and renal failure elicited by lipoteichoic acid (LTA) from Staphylococcus aureus (an organism without endotoxin) in anaesthetized rats. Administration of LTA (10 mg kg−1, i.v.) caused hypotension and vascular hyporeactivity to noradrenaline (1 μg kg−1, i.v.). WEB2086 (5 mg kg−1, i.v., 20 min before and 150 min after LTA) inhibited the delayed fall in mean arterial blood pressure (at 300 min: 99 ±6 mmHg vs. 75 ±6 mmHg, P<0.01) and prevented the decrease in pressor response to noradrenaline (at 300 min: 36 ±5 mmHg min vs. 17±5 mmHg min, P<0.01). Surprisingly, BN52021 (20 mg kg−1, i.v., 20 min before and 150 min after LTA) neither prevented the hypotension (74±6 mmHg) nor the vascular hyporeactivity (21±5 mmHg min). However, BN52021 inhibited the hypotension to injections of PAF as well as the circulatory failure elicited by lipopolysaccharides (10 mg kg−1, i.v.). LTA caused an increase in plasma concentration of creatinine from 39±5 μm (sham‐operated) to 70±8 μm and urea from 4.7±0.1 to 13.1±1.6 mM. The renal failure elicited by LTA was significantly inhibited by WEB2086 (creatinine: 45±4 μm and urea: 5.7±0.7 mM), but not by BN52021. The induction of nitric oxide synthase activity in lungs by LTA was attenuated by WEB2086 from 98±17 to 40±15 pmol L‐citrulline 30 min−1 mg−1 protein (P<0.01), but not by BN52021 (148±21 pmol L‐citrulline 30 min−1 mg−1 protein). Similarly, WEB2086, but not BN52021, inhibited the increase in plasma nitrite concentration associated with the delayed circulatory failure caused by LTA. The release of tumour necrosis factor‐α (TNF‐α) after injection of LTA was not attenuated by WEB2086. The induction of nitrite release by cultured macrophages activated with LTA (10 μg ml−1 for 24 h) was inhibited by 74±4% by WEB2086 (3times10−4 m), but not by BN52021, indicating that only WEB2086 acts on intracellular PAF receptors. Thus, the intracellular release of PAF contributes to the circulatory and renal failure and induction of nitric oxide synthase elicited by LTA in anaesthetized rats. The difference between the two structurally different PAF antagonists in our septic shock models using either LTA or lipopolysaccharide (LPS), shows the importance of models for Gram‐positive sepsis in the elucidation of the pathophysiology of septic shock and for the evaluation of potential drugs.

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Section: Tnf-ca Measurementsmentioning

confidence: 76%

Section: Tnf-ca Measurementsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Role for intracellular platelet‐activating factor in the circulatory failure in a model of Gram‐positive shock

Kimpe¹,

Thiemermann

Vane

1995

British J Pharmacology

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“…The structures and relative potencies of these diverse compounds have been previously reviewed in detail (Hwang, 1994;Koltai et al, 1994;Negro Alvarez et al, 1997). Many PAF antagonists have been extensively evaluated in studies designed to identify an etiological role for PAF in experimental animal models of human disease.…”

Section: (E) Paf In Bone Biologymentioning

confidence: 99%

PAF, a Putative Mediator of Oral Inflammation

McManus

Pinckard

2000

Critical Reviews in Oral Biology & Medicine

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PAF, or platelet-activating factor, is a family of structurally related phospholipids (1 -O-alkyl/acyl/alkenyl-2-acetylsn-glycero-3-phosphocholine) which possesses a wide spectrum of potent pro-inflammatory actions. These phospholipids are synthesized by a diverse array of cells, including neutrophilic polymorphonuclear leukocytes (PMN), platelets, mast cells, monocytes/macrophages, vascular endothelial cells, and lymphocytes. PAF targets these and other cells via specific, G-proteincoupled receptors to initiate intracrine, autocrine, paracrine, and juxtacrine cell activation. Of importance, these unique acetylated phospholipids are frequently synthesized in concert with pro-inflammatory lipid mediators derived from arachidonic acid. Since PAF synergizes with these and other mediators to amplify the inflammatory response, it seems likely that PAF plays an integral, perhaps pivotal, role in acute and chronic inflammatory processes. PAF is present in the mixed saliva of dentate, but not edentulous, human subjects. The levels of PAF in mixed saliva or in gingival crevicular fluid and tissues are significantly increased during oral inflammatory conditions such as periodontitis and mucositis. Interestingly, the levels of salivary PAF correlate with the extent/severity of these oral diseases. These observations suggest that PAF may participate in pathophysiologic events during the course of oral inflammation. The availability of specific PAF receptor antagonists and human recombinant PAF-acetylhydrolase (PAF-AH), a plasma enzyme which rapidly destroys PAF, should provide clinical tools for the investigation of the role of PAF in these and other inflammatory disorders; and perhaps, ultimately, some of these reagents may prove to be therapeutically useful in the treatment and management of these conditions.

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“…For example, a lipo-PGEl preparation (Green Cross Co.) represents PGE 1 incorporated into lipid particles with the dimensions 0.2 -0.4 ~j_rn [50]. PGE 1 entering into the composition of lipo-PGEl is stable with respect to inactivation and degradation in lungs, while the small dimensions of particles allow them to penetrate via blood vessels into damaged tissues and produce considerable therapeutic effect [50].…”

mentioning

confidence: 99%

Lipid derivatives of prostaglandins and nonsteroidal antiinflammatory drugs (a review)

Kulikov

Muzya

1997

Pharm Chem J

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, and phospholipids with ether and thioester bonds [7,8], and antibiotic mitomycin C conjugated with cholesteryloxycarbonylglycine [9]. The other group includes synthesized and characterized lipid derivatives of antiviml preparations such as acyclovir [10], phosphonoformate [11], and azidothymidine, dideoxycytidine, and dideoxythymidine known to be highly active with respect to the human immunodeficiency virus (HIV) [12]. Transformation of 7-aminobutyric acid (GABA) into 1,2-dipalmitoylglyceric or 1-acylglyceric esters allowed the concentration of this neuromediator in the brain to be increased by more than two orders of magnitude [13 -15]. Other promising directions are the modification of immunoglobulins [ 16], bacterial antigens and vaccinal preparations [17,18] that in many cases makes it possible to increase their efficiency. This work is not an attempt to consider and summarize the results of all investigations devoted to the lipophilic modification of biologically active compounds (including drugs) because these objects are rather dissimilar and differ markedly in their spectra and mechanisms of action. The purpose of this review is to demonstrate the possibilities and prospects of the lipophilic modification of biologically active compounds in the case of prostaglandins and nonsteroidal antiinflammatory drugs. The choice of these groups of biologically active compounds is mostly due to the fact

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Paf

Cited by 112 publications

References 262 publications

Role for intracellular platelet‐activating factor in the circulatory failure in a model of Gram‐positive shock

Role for intracellular platelet‐activating factor in the circulatory failure in a model of Gram‐positive shock

PAF, a Putative Mediator of Oral Inflammation

Lipid derivatives of prostaglandins and nonsteroidal antiinflammatory drugs (a review)

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