Platelets in the immune response: Revisiting platelet-activating factor in anaphylaxis.

Abstract

Anaphylaxis is an acute, severe, life-threatening multisystem allergic reaction resulting from the sudden systemic release of biochemical mediators and chemotactic substances. Release of both preformed granule-associated mediators and newly generated lipid-derived mediators contributes to the amplification and prolongation of anaphylaxis. Platelet-activating factor (PAF) is a potent phospholipid-derived mediator the central role of which has been well established in experimental models of both immune-mediated and non-immune mediated anaphylaxis. It is produced and secreted by several types of cells, including mast cells, monocytes, tissue macrophages, platelets, eosinophils, endothelial cells, and neutrophils. PAF is implicated in platelet aggregation and activation through release of vasoactive amines in the inflammatory response, resulting in increased vascular permeability, circulatory collapse, decreased cardiac output, and various other biological effects. PAF is rapidly hydrolyzed and degraded to an inactive metabolite, lysoPAF, by the enzyme PAF acetylhydrolase, the activity of which has shown to correlate inversely with PAF levels and predispose to severe anaphylaxis. In addition to its role in anaphylaxis, PAF has also been implicated as a mediator in both allergic and nonallergic inflammatory diseases, including allergic rhinitis, sepsis, atherosclerotic disease, and malignancy, in which PAF signaling has an established role. The therapeutic role of PAF antagonism has been investigated for several diseases, with variable results thus far. Further investigation of its role in pathology and therapeutic modulation is highly anticipated because of the pressing need for more selective and targeted therapy for the management of severe anaphylaxis.

• Authors: Parwinder Gill, Nina Lakhani Jindal, Amanda Jagdis, Peter Vadas
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 135 Issue 6 Pg. 1424-32 (Jun 2015) ISSN: 1097-6825 [Electronic] United States
• PMID: 26051949 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Platelet Activating Factor
• Platelet Membrane Glycoproteins
• Receptors, G-Protein-Coupled
• platelet activating factor receptor
• 1-Alkyl-2-acetylglycerophosphocholine Esterase

Topics

• 1-Alkyl-2-acetylglycerophosphocholine Esterase (genetics, immunology)
• Anaphylaxis (genetics, immunology, pathology)
• Asthma (genetics, immunology, pathology)
• Blood Platelets (immunology, pathology)
• Eosinophils (immunology, pathology)
• Gene Expression Regulation
• Humans
• Mast Cells (immunology, pathology)
• Neutrophils (immunology, pathology)
• Platelet Activating Factor (genetics, immunology)
• Platelet Activation (genetics, immunology)
• Platelet Aggregation (genetics, immunology)
• Platelet Membrane Glycoproteins (genetics, immunology)
• Receptors, G-Protein-Coupled (genetics, immunology)
• Sepsis (genetics, immunology, pathology)
• Signal Transduction