Platelet Activating Factor (PAF)

Abstract

This review is an attempt to summarise recent data on platelet activating factor (PAF) and PAF antagonists from 1988 to the present. This period saw a burst in research activity focused predominantly on the effect of PAF in various organs. The effect of PAF and its antagonists was further intensively studied in vitro on isolated platelets, leucocytes, macrophages and endothelial cells. From these and earlier data, based on the catastrophe theory of Thom and Zeeman, a new concept on the interaction between PAF and various cytokines could be recognised as an important mechanism of action of the phospholipid mediator, suggesting the existence of an autocatalytic feedback network through which PAF can influence cellular function under certain pathophysiological conditions. This mechanism can be regarded as the culmination of our recent knowledge on the role of PAF, and may influence the possible clinical implications of PAF antagonists in the near future. It is recognised that PAF is released in shock and ischaemic states, and that PAF antagonists can protect the heart and brain against ischaemic injury. Therefore, in contrast to the previous period, which was predominantly devoted to the elucidation of the role of PAF in immediate hypersensitivity reactions, studies performed on cerebral, myocardial and intestinal ischaemia as well as in various shock conditions have concentrated on entirely new aspects of the effect of PAF antagonists, emphasising the significance of the inflammatory process and cell-to-cell interactions in these pathophysiological states. This has led to a re-evaluation of the experimental data previously accumulated. At the same time, these new trends in PAF and PAF antagonist research have explored further possibilities for the application of PAF antagonists in clinical practice. Attention has been focused on the physiological role of PAF as a signal molecule, especially between the neuroendocrine system and related sensory organs. The recognition of the significance of PAF in mammalian reproduction is fascinating and may lead to new clinical applications of PAF antagonists. It appears probable that, like eicosanoids, PAF is involved in a great variety of membrane-dependent processes that play a fundamental role in the maintenance of homeostasis. PAF research has provided several potent natural and synthetic antagonists which may facilitate the clinical application of these drugs in the near future.

Platelet-Activating Factor Antagonist BN 50730 Attenuates Hypoxic-Ischemic Brain Injury in Neonatal Rats

“…BN 50730 was a gift from Dr. N. Bazan (Louisiana State University Neuroscience Center, New Orleans, LA, U.S.A.). The structure of this hetrazepine compound has been published by other investigators (33).…”

The Role of Inflammatory Mediators in the Pathogenesis of Otitis Media and Sequelae

“…TNF also stimulates synthesis of IL-1 (14). Platelet activating factor (PAF) can enhance IL-1 release by the production of leukotriene metabolites (34). IL-1β is mainly produced and released extracellularly by inflammatory cells such as macrophages/monocytes (35) and IL-1α is localized intracellularly or on the surface of such cells (36).…”

Is sepsis a mediator-inhibitor mismatch?

“…Both intrinsic and extrinsic systems are activated, and this activation is followed by platelet and fibrinolytic system activations with the release of inflammatory mediators (kinins, PAF, thromboxane, etc.) and proteases (kallikrein, factors XIIa, VfIa, thrombin, plasmin) [55]. Antithrombin III, antiplasmin and other antiproteinases such as a2 macroglobulin are natural defenses against coagulation proteases, but these are likely to be rapidly overwhelmed, despite their important concentrations in plasma, as excessive coagulation phenomena are common during sepsis and SIRS.…”