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Forty Years Since the Structural Elucidation of Platelet-Activating Factor (PAF): Historical, Current, and Future Research Perspectives - PubMed

  • ️Tue Jan 01 2019

Review

Forty Years Since the Structural Elucidation of Platelet-Activating Factor (PAF): Historical, Current, and Future Research Perspectives

Ronan Lordan et al. Molecules. 2019.

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.

Keywords: cardiovascular disease; cell signalling; inflammation; phospholipids; platelet-activating factor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1

The structure of platelet-activating factor (PAF): (A) PAF space fill model data from [42] and (B) PAF structural model.

Figure 2
Figure 2

The main biosynthetic and degradation pathways of PAF. The red underlined enzymes are the regulatory enzymes of PAF synthesis.

Figure 3
Figure 3

A simplified schematic that illustrates the main pro-inflammatory signalling pathways that PAF induces through binding with its receptor under certain stresses or stimuli in various pathways and inflammatory cascades in inflammation-related chronic disorders.

Figure 4
Figure 4

Representative optic micrographs ×100 of aortic wall sections stained with hematoxylin and eosin obtained from the two rabbit experimental groups. Atherosclerotic lesions appear as foam cells between the arrows. Each tissue sample was approximately 5 µm thick. (a) Group A (atherogenic diet) and (b) group B (atherogenic diet enriched with seabream polar lipids). Reproduced with permission from Nasopoulou et al. [220].

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