Biological Properties of Platelet-Activating Factor

Stewart, Geoffrey A.

doi:10.1016/b978-0-12-198875-3.50014-1

Cited by 10 publications

(7 citation statements)

References 658 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, elucidation of the role of oxidized-PC in the pathogenesis of atherogenesis warrants further study. Moreover, it has been suggested that cigarette smoking might lead to formation of the oxidized-PC in LDL (Stewart, 1994;FitzGerald, 1997;Lehr et al, 1997). Fortunately, oxidized-PC generated from LDL would be rapidly degraded to lyso-PC by a plasma enzyme, PAF-AH (see below), which is also present in LDL Stafforini et al, 1992).…”

Section: (I) Introductionmentioning

confidence: 99%

PAF, a Putative Mediator of Oral Inflammation

McManus

Pinckard

2000

Critical Reviews in Oral Biology & Medicine

View full text Add to dashboard Cite

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.

show abstract

Section: (I) Introductionmentioning

confidence: 99%

PAF, a Putative Mediator of Oral Inflammation

McManus

Pinckard

2000

Critical Reviews in Oral Biology & Medicine

View full text Add to dashboard Cite

show abstract

“…Numerous studies have reported the role of PAF [1] in eliciting strong inflammatory responses [2,3]. PAF is produced by a variety of cell types relevant to inflammation including macrophages, neutrophils, eosino phils, basophils, mast cells, and vascular endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…It is released from most inflam matory cells by various immunological and nonimmunological stimuli and acts on the same target cells. PAF stimulates neutrophil chemotaxis and promotes secretion of granular constituents with release of lysosomal enzymes and free redicals [3]. PAF has been implicated in the patho genesis of various inflammatory conditions, but its pres ence is ill-documented in well-defined models of local in flammation.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Tissue Levels of Histamine, PAF-Acether and Lysopaf-Acether in Carrageenan-lnduced Granuloma in Rats

Aïssa

Harran²,

Rabeau³

et al. 1996

Int Arch Allergy Immunol

View full text Add to dashboard Cite

The tissue concentrations of several inflammatory mediators were determined from day 0 to day 60 in granuloma induced in rats (n = 105) by injection of carrageenan in the fascia of the latissimus dorsi muscle. Noncollagen proteins (NCP) and the number of polymorphonuclear leukocytes (PMN) and mast cells were also assessed. In comparison with the tissue at time 0, we noted in the inflamed tissue (at 4 h) an increase in total proteins (4.0 ± 3.0 vs. 84 ± 12.0%, mean ± SEM) and PMN (0.0 ± 0.0 vs. 43.3 ± 13.4%), and a fall in histamine concentration (from 30.0 ± 9.0 to 9.0 ± 4.0 ng/ml). A partial disappearence of mast cells and an increase of PAF-acether (PAF) levels (1.0 ± 1.0 vs. 30.0 ± 22.0 ng/ml) was noted at 16 h, whereas lysopaf remained unchanged (3.7 ± 4.0 vs. 3.5 ± 1.0 ng/ml). During evolution towards chronic inflammation (day 10–60), NCP decreased, PMN disappeared and mast cells reapeared; the histamine level rose to 11.0 ± 2.0 mg/ml, thus not reaching back baseline values. Lysopaf rose to 7.1 ± 12.2 ng/ml and PAF levels increased further to reach 240.0 ± 153.0 ng/ml at day 10. This study suggests that PAF may contribute to the acute phase of an inflammatory state such as the carrageenan-induced granuloma and that it is also present during the chronic process.

show abstract

“…Platelet-activating factor (PAF) is a proinflammatory mediator which has been impli cated in a number of animal models of disease processes, including sepsis, ischaemia/reperfusion injury, and asthma [1]. This phospho lipid-derived mediator stimulates generation of superoxide anion (Oi) in guinea pig macro phages [2] and aggregation of human periph eral blood monocytes [3], It is of considerable interest that while PAF does not stimulate Oi generation in mu rine resident peritoneal macrophages, there is convincing evidence for the presence of PAF receptors linked to phospholipase C activa tion on these cells [4,5].…”

Section: Introductionmentioning

confidence: 99%

Role of Tyrosine Phosphorylation in the Signalling of Superoxide Anion Generation in Platelet-Activating-Factor-Stimulated Peritoneal Macrophages

Grigoriadis¹,

Stewart²

1996

Cell Physiol Biochem

View full text Add to dashboard Cite

The signalling pathway(s) involved in the activation of superoxide anion (O^–₂) generation by platelet-activating factor (PAF) are not well understood, But elevations of sn-l,2-diacylglycerol and intracellular calcium contribute to activation by stimulating protein kinase C activity. Since recent studies have suggested that tyrosine phosphorylation may also be a component of the signalling of O^–₂ generation in human neutrophils, we have investigated whether PAF stimulates tyrosine phosphorylation in guinea pig and rat macrophages. PAF (10 nM) stimulated tyrosine phosphorylation within 10–30 s, coinciding with the onset of the O^-₂ generation in guinea pig peritoneal macrophages. At 30 min after exposure of guinea pig macrophages to PAF, the phosphorylation levels were similar to those of unstimulated cells. In contrast, in rat peritoneal macrophages, PAF did not stimulate tyrosine phosphorylation of high molecular weight proteins, nor did it elicit the generation of O^–₂. PAF-induced O^–₂ generation was inhibited by pre-treatment of guinea pig peritoneal macrophages with the protein tyrosine kinase inhibitors methyl 2, 5-dihydroxymethylcinnamate and tyrphostin. The qualitative difference between PAF-induced phosphorylation patterns in rat and guinea pig macrophages and the inhibitory effects of protein tyrosine kinase inhibition are consistent with an important role for protein tyrosine kinase(s) in O^–₂ generation.

show abstract

Biological Properties of Platelet-Activating Factor

Cited by 10 publications

References 658 publications

PAF, a Putative Mediator of Oral Inflammation

PAF, a Putative Mediator of Oral Inflammation

Tissue Levels of Histamine, PAF-Acether and Lysopaf-Acether in Carrageenan-lnduced Granuloma in Rats

Role of Tyrosine Phosphorylation in the Signalling of Superoxide Anion Generation in Platelet-Activating-Factor-Stimulated Peritoneal Macrophages

Contact Info

Product

Resources

About