Peripheral mediators can contribute to the development and maintenance of inflammatory and neuropathic pain and its concomitants (hyperalgesia and allodynia) via two mechanisms. Activation or excit...

Sensory and signaling mechanisms of bradykinin, eicosanoids, platelet-activating factor, and nitric oxide in peripheral nociceptors

Platelet-activating factor (PAF) is an inflammatory mediator that causes bronchial smooth muscle contraction in vitro and in vivo in experimental animals. To characterize the effect of PAF on human airways, 6 normal subjects and 6 subjects with mild asthma inhaled PAF using a standard bronchoprovocation protocol and nebulizer concentrations ranging from 0.1 to 1000 ng/ml. Aerosolized PAF produced bronchoconstriction in 5 of 6 normal and 3 of 6 asthmatic subjects as defined by at least a 35% decrease in specific airway conductance (SGaw). However, in these same subjects, flow rates measured at 30% of vital capacity from a partial forced expiratory maneuver (30P) did not decrease at least 30% nor did the FEV1 decrease by 20%. The 8 PAF responders were 5 to 836 times more sensitive to PAF than to methacholine when SGaw was used to assess the airway response. The relative airway sensitivity of the PAF nonresponders could not be assessed. Normal and asthmatic subjects could not be differentiated by their airwa...

The bronchoconstrictor properties of platelet-activating factor in humans.

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.

https://www.mdpi.com/1420-3049/24/23/4414/pdf

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

Paf-acether: a mediator of inflammation and asthma

Bronchoconstriction and degenerative lesions of the bronchial epithelium were observed microscopically 1 min after the i.v. injection of 100 ng/kg of platelet-activating factor (PAF-acether) to the anaesthesized guinea-pig. Constricted arterioles containing marginated polymorphonuclear neutrophils and platelet aggregates were seen, as well as alveolar capillaries obstructed by thrombi formed by partially or totally degranulated platelets. Three minutes after the injection of PAF-acether, platelet diapedesis to the alveolar septa and lumen was clearly observed. Bronchoconstriction was still present at 3 min, but subsided after 60 min, whereas oedema of the submucosa persisted accompanied by an infiltration of eosinophils and neutrophils. The infusion of prostacyclin prevented the formation of platelet aggregates and platelet diapedesis due to PAF-acether, but the morphological evidence of bronchial constriction was not modified. Aspirin failed completely to modify the effects of PAF-acether. Our results show that PAF-acether causes early formation and deposition of platelet aggregates, accompanied by the margination of polymorphonuclear neutrophil leucocytes in pulmonary vessels of the guinea-pig. Since bronchoconstriction persisted when platelet aggregation was inhibited with prostacyclin, aggregation by itself would not account for this effect. Early platelet diapedesis in the vicinity of bronchial smooth muscle corroborates previous evidence that platelets contain and release bronchoconstrictor substances, which operate by cyclo-oxygenase-independent mechanisms and are possibly involved with the physiopathology of lung inflammation during immediate hypersensitivity.

Ultrastructural evidence for extravascular platelet recruitment in the lung upon intravenous injection of platelet-activating factor (PAF-acether) to guinea-pigs.

Certain allergic asthmatic patients exhibit a dual response in the lung following bronchial challenge with the appropriate allergen. Often this is paralleled by a cutaneous dual response when the antigen is injected intradermally. The mechanisms underlying such phenomena are not established, but some evidence suggests that the late response is a consequence of the early response. Since platelet activation has been observed following antigen challenge in asthmatic subjects, we have studied the ability of platelet activating factor (PAF-acether, AGEPC) to induce cutaneous inflammatory responses in man. In a time course study over 24 hr, PAF-acether produced a biphasic response: an immediate weal and flare reaction, which resolved within 1-2 hr and was followed some 3-6 hr later by a delayed reaction in which erythema associated with hyperalgesia was evident. These observations suggest that PAF-acether should be considered in the context of allergic asthma as a possible mediator of the dual response to allergen.

Platelet‐activating factor: a possible mediator of the dual response to allergen?

PAF-acether: a putative mediator of asthma and inflammation.

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Platelet‐activating factor: a possible mediator of the dual response to allergen?

PAF-acether: a putative mediator of asthma and inflammation.