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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:135

Article

Gill, Parwinder¹  Jindal, Nina Lakhani¹  Jagdis, Amanda²  Vadas, Peter¹ 

[1] Univ Toronto, St Michaels Hosp, Div Clin Immunol & Allergy, Toronto, ON M5B 1W8, Canada

[2] Univ British Columbia, Div Allergy & Immunol, Vancouver, BC V5Z 1M9, Canada

关键词: Allergy;    anaphylaxis;    mast cells;    platelet-activating factor;    acetylhydrolase;    signaling;    receptor antagonists;    platelets;    sepsis;    mediators;   

DOI  :  10.1016/j.jaci.2015.04.019

来源: Elsevier

【 摘 要 】

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.

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