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Review
. 2021 Mar 15:12:624132.
doi: 10.3389/fendo.2021.624132. eCollection 2021.

New Insights Into the Pathologic Roles of the Platelet-Activating Factor System

Jeffrey B Travers  1   2   3 , Joyce G Rohan  4 , Ravi P Sahu  1
Affiliations
Review

New Insights Into the Pathologic Roles of the Platelet-Activating Factor System

Jeffrey B Travers et al. Front Endocrinol (Lausanne). .

Abstract

Described almost 50 years ago, the glycerophosphocholine lipid mediator Platelet-activating factor (PAF) has been implicated in many pathologic processes. Indeed, elevated levels of PAF can be measured in response to almost every type of pathology involving inflammation and cell damage/death. In this review, we provide evidence for PAF involvement in pathologic processes, with focus on cancer, the nervous system, and in photobiology. Importantly, recent insights into how PAF can generate and travel via bioactive extracellular vesicles such as microvesicle particles (MVP) are presented. What appears to be emerging from diverse pathologies in different organ systems is a common theme where pro-oxidative stressors generate oxidized glycerophosphocholines with PAF agonistic effects, which then trigger more enzymatic PAF synthesis via the PAF receptor. A downstream consequence of PAF receptor activation is the generation and release of MVP which provide a mechanism to transmit PAF as well as other bioactive agents. The knowledge gaps which when addressed could result in novel therapeutic strategies are also discussed. Taken together, an enhanced understanding of the PAF family of lipid mediators is essential in our improved comprehension of the relationship amongst the diverse cutaneous, cancerous, neurologic and systemic pathologic processes.

Keywords: cancer; central nervous system; inflammation; microvesicle particles; oxidized glycerophosphocholine; platelet-activating factor (PAF); skin; ultraviolet - B.

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Conflict of interest statement

JR is an employee of the U.S. Government. This work was prepared as part of her official duties. Title 17, USC, §105 provides that ‘Copyright protection under this title is not available for any work of the U.S. Government.’ Title 17, USC, §101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person’s official duties. This research was supported in part by grants from the National Institutes of Health grant R01 HL062996 (JT), Veteran’s Administration Merit Award 5I01BX000853 (JT). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The views expressed in this presentation are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government.

Figures

Figure 1
Figure 1
Hypothetical model by which UVB generates PAFR agonists via ROS which then result in PAF-laden MVP release. In this model, ROS generated by UVB result in ox-GPC as well as enzymatic PAF synthesis. These PAFR agonists act upon the PAFR resulting in MVP generation release via acid sphingomyelinase activation. These MVP contain bioactive agents, especially PAFR agonists which then can mediate UVB effects.
See this image and copyright information in PMC

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