PAF, a Putative Mediator of Oral Inflammation

Abstract

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.

Platelet-Activating Factor-Acetylhydrolase Can Monodeacylate and Inactivate Lipoteichoic Acid

“…PAF-AH is a phospholipase A2 (PLA2) and inactivates PAF by removing the acetyl group at the sn-2 position (3,11,27,34,37). In addition to PAF, PAF-AH can remove acyl chains at the sn-2 position from various glycerolipids, including diacylglycerols, triacylglycerols, and acetylated alkanols (28).…”

Influence of platelet-activating factor, lyso-platelet-activating factor and edelfosine on Langmuir monolayers imitating plasma membranes of cell lines differing in susceptibility to anti-cancer treatment: the effect of plasmalogen level

“…Interestingly, there is strong evidence that ether lyso-lipids disclose their activities either by binding with a specific receptor localized in cellular membrane [7][8][9] or by direct incorporation into the lipid bilayer [10][11][12]. The second mechanism is possible due to the amphiphatic character of PAF and its lyso-derivative possessing predominantly long saturated C16 or C18 hydrocarbon chains [13]. Besides the above-mentioned natural single-chained ether phospholipids, their synthetic analogues of anti-cancer properties, called alkyl-lysophospholipids, have been synthesized.…”

Delineation of the Role of Platelet-Activating Factor in the Immunoglobulin G2 Antibody Response

“…The potential connection between PAF and periodontitis was recognized as far back as 1989, when it was reported that PAF levels were elevated in inflamed gingival tissues (37). Since that initial report, elevated PAF levels have been demonstrated in the saliva, gingival crevicular fluid, and gingival tissues of periodontitis patients (18,35), including subjects with LAgP. It is likely that the high levels of PAF observed in LAgP and other periodontal diseases are at least partially due to increased synthesis, as activated inflammatory cells are the primary sources of PAF (40).…”

“…Thus, we predict that the skewing of monocyte differentiation in LAgP subjects results in low levels of the catabolic enzyme PAFAH and that this allows the bioactive lipid PAF to accumulate and thereby activate inflammatory cells. A positive correlation has been observed between PAF levels and disease severity, which suggests that PAF may have a causative role in the disease process (21,35). Indeed, periodontal therapies not only reduce the indices of disease but also result in reductions in salivary PAF (41).…”

“…The PAF-induced Th1 response culminates in the production of gamma interferon (IFN-␥), the cytokine most closely associated with IgG2 production (30,31). Given the elevated levels of PAF that are present in the cells and tissues of periodontitis patients (18,21,35,37), this may account for the high levels of IgG2 that are present in their sera.…”