PAF, a putative mediator of oral inflammation.
PAF, or platelet-activating factor, is a family of structurally related phospholipids (1-O-alkyl/acyl/alkenyl-2-acetyl-sn-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-protein-coupled 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.
McManus
L M
LM
Department of Pathology, The University of Texas Health Science Center, San Antonio 78229, USA. mcmanus@uthscsa.edu
Pinckard
R N
RN
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000208:Acute Disease; D001095:Arachidonic Acids / Q000502:physiology; D019898:Autocrine Communication / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002908:Chronic Disease; D019204:GTP-Binding Proteins / Q000502:physiology; D005883:Gingival Crevicular Fluid / Q000737:chemistry; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology; D019899:Paracrine Communication / Q000502:physiology; D010518:Periodontitis / Q000378:metabolism; D010741:Phospholipases A / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D012463:Saliva / Q000737:chemistry; D013280:Stomatitis / Q000209:etiology* / Q000378:metabolism
D001095:Arachidonic Acids; D018836:Inflammation Mediators; D010972:Platelet Activating Factor; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D019204:GTP-Binding Proteins