BN 52021 (a platelet activating factor-receptor antagonist) decreases alveolar macrophage-mediated lung injury in experimental extrinsic allergic alveolitis

Abstract

SEVERAL lines of research indirectly suggest that platelet activating factor (PAF) may intervene in the pathogenesis of extrinsic allergic alveolitis (EAA), The specific aim of our study was to evaluate the participation of PAF on macrophage activation during the acute phase of EAA in an experimental model of this disease developed in guinea pigs, Initially we measured the concentration of PAF in bronchoalvedar lavage fluid, blood and lung tissue, In a second phase we evaluate the participation of PAF on alveolar macrophage activation and parenchymal lung injury. The effect of PAF on parenchymal lung injury was evaluated by measuring several lung parenchymatous lesion indices (lung index, bronchoalvedar lavage fluid (BALF) lactic hydrogenase activity and BALF alkaline phosphatase activity) and parameters of systemic response to the challenge (acute phase reagents), We observed that induction of the experimental EAA gave rise to an increase in the concentration of PAF in blood and in lung tissue. The use of the PAF-receptor antagonist BN52021 decreases the release of lysosomal enzymes (beta-glucuronidase and tartrate-sensitive acid phosphatase) to the extracellular environment both in vivo and in vitro. Furthermore, antagonism of the PAF receptors notably decreases pulmonary parenchymatous lesion. These data suggest that lung lesions from acute EAA are partly mediated by local production of PAF.