Abstract
In the late 1960s, Barbaro and Zvaifler described a substance that caused antigen induced histamine release from rabbit platelets producing antibodies in passive cutaneous anaphylaxis. Henson described a ‘soluble factor’ released from leukocytes that induced vasoactive amine release in platelets. Later observations by Siraganuan and Osler observed the existence of a diluted substance that had the capacity to cause platelet activation. In 1972, the term platelet-activating factor (PAF) was coined by Benveniste, Henson, and Cochrane. The structure of PAF was later elucidated by Demopoulos, Pinckard, and Hanahan in 1979. These studies introduced the research world to PAF, which is now recognised as a potent phospholipid mediator. Since its introduction to the literature, research on PAF has grown due to interest in its vital cell signalling functions and more sinisterly its role as a pro-inflammatory molecule in several chronic diseases including cardiovascular disease and cancer. As it is forty years since the structural elucidation of PAF, the aim of this review is to provide a historical account of the discovery of PAF and to provide a general overview of current and future perspectives on PAF research in physiology and pathophysiology.
Highlights
It is clear that the discovery and structural elucidation of platelet-activating factor (PAF) sparked major interest into the role of PAF in physiology and pathophysiology, along with lipid mediators in general from the 1970s onwards
It is clear from the wealth of evidence presented that understanding the mechanisms of PAF/PAF-R signalling in health and disease has yet to be fully elucidated
The discovery of various PAF and PAF-like lipids (PAFLL) agonists and antagonists, the role of the PAF metabolic enzymes in diseases, solving the human PAF-R structure, and identifying PAF signalling mechanisms independent of the PAF-R are some of the many major achievements in current PAF research
Summary
The structure of platelet-activating factor (PAF) known as PAF-acether or AGEPC (acetyl-glyceryl-ether-phosphorylcholine) has been identified as a phosphoglycerylether lipid mediator involved in diverse physiological and pathophysiological processes. PAF has different physiological roles in animals, plants, and monocellular organisms It is considered the most potent lipid mediator known to date [1,2]. For the purpose of this review, PAF refers to the classical structure reported in 1979, which is responsible for most of the known biological effects and is thought to be the most potent PAF molecule. Many ether lipids were replaced over time by their esterified analogues; PAF and other minor phosphoglycerylether molecules were conserved in various organisms due to their important biological roles [15]. The aim of this review is to provide a historical account on the discovery of PAF, the research conducted since, and to provide future research perspectives on PAF research in general
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