BN-52021 (A PLATELET-ACTIVATING FACTOR-RECEPTOR ANTAGONIST) DECREASESALVEOLAR MACROPHAGE-MEDIATED LUNG INJURY IN EXPERIMENTAL EXTRINSIC ALLERGIC ALVEOLITIS

SEVERAL lines of research indirectly suggest that platelet activating factor (PAF) may intervene in the pathogenesis of extrinsic allergic a lveolitis (EAA), The specific aim of our study was to evaluate the par ticipation of PAF on macrophage activation during the acute phase of E AA in an experimental model of this disease developed in guinea pigs, Initially we measured the concentration of PAF in bronchoalvedar lavag e fluid, blood and lung tissue, In a second phase we evaluate the part icipation of PAF on alveolar macrophage activation and parenchymal lun g injury. The effect of PAF on parenchymal lung injury was evaluated b y measuring several lung parenchymatous lesion indices (lung index, br onchoalvedar 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 th e experimental EAA gave rise to an increase in the concentration of PA F 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 environ ment both in vivo and in vitro. Furthermore, antagonism of the PAF rec eptors notably decreases pulmonary parenchymatous lesion. These data s uggest that lung lesions from acute EAA are partly mediated by local p roduction of PAF.