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.
Highlights
The term “platelet-activating factor” was first given by Benveniste and colleagues in their landmark Journal of Experimental Medicine manuscript in 1972, to a biochemical activity released by activated basophils which caused platelets to aggregate [1]
Given that murine Myeloid-derived suppressor cells (MDSCs) express CD11b and Gr-1 surface markers, and that their depletion have been explored as potential therapeutic approaches against solid tumors, we evaluated its role in mediating PAF receptor (PAFR)-dependent tumor growth
Our studies found that UVB- or CPAF-mediated increased growth of B16F10 melanoma tumors was blocked by depleting MDSCs [63]
Summary
Described almost 50 years ago, the glycerophosphocholine lipid mediator Plateletactivating factor (PAF) has been implicated in many pathologic processes. We provide evidence for PAF involvement in pathologic processes, with focus on cancer, the nervous system, and in photobiology. 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 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. 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
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