The action of platelet activating factor and its antagonism by WEB 2086 on human isolated airways

Abstract

This study investigated the direct and indirect effects of platelet activating factor (PAF, PAF-acether) on human isolated airways. PAF caused a single non-repeatable contraction which was found to be variable both between lung samples and within tissues from the same lung. The range of contractions induced by PAF, 7 X 10(-8), M and 7 X 10(-7) M was 2-55% and 3-72% of the maximal response to carbachol, respectively. The PAF antagonist WEB 2086, 10(-6) M, inhibited the contraction induced by PAF, 7 X 10(-7) M, (p less than 0.05, n = 5). PAF caused a significant potentiation of the contractile effects of bolus doses of histamine. This potentiation was inhibited by WEB 2086, 10(-6) M, (p less than 0.05, n = 5). These results suggest firstly that the bronchoconstriction observed in man after PAF administration could be the result of an action of PAF on the smooth muscle or result from the action of a second mediator released by PAF from cells within the lung. Secondly, the bronchial hyperresponsiveness observed after PAF administration could be due to a specific alteration in smooth muscle sensitivity. The fact that WEB 2086 inhibited the contractile response to PAF and the potentiation of histamine-induced contraction would suggest that PAF receptors mediate these responses.

Does airway smooth muscle care about platelet-activating factor?

“…that contraction of human isolated bronchus induced by PAF is not related to the release of mediators [Tom secondary cells. Hence, the variability of the responses to PAP, observed in this study and previous studies [25,30] may not be due to bronchial tissue dwelling cells but rather to a direct effect of the mediator.…”

“…Clearly, more studies are needed before the conclusions drawn by JoHNSON et al [29,30] can be fully accepted. Whether or not airway smooth muscle is affected by PAF directly, the potential s ignificance of PAF remains.…”

Platelet-activating factor-induced contraction of human isolated bronchus

“…The variability in the PAP responses observed in vivo [7,18] and in vitro [4] suggests that PAF may be having an indirect mode of action. SMITH et al [7) observed intersubject variability in the PAF response in vivo, which they suggested was due to an indirect mechanism of action of PAF.…”

“…We have previously shown that PAF causes a variable contraction of human isolated airways [4] . Because of the variable nature of this response, we propose that the in vitro PAP-induced effects are secondary to the release of mediators from inflammatory or epithelial cells .…”

“…Platelet-activating factor (PAF) is a naturally occurring phospholipid, which causes bronchoconstriction and a contraction of isolated airway tissue from animals [1 , 2] and man [3,4]. The mechanism by which P AF produces these effects both in vivo and in vitro is unknown, however, a number of inflammatory mediators have been implicated.…”