Potential Role Of Platelet-Activating Factor In Development Of Occupational Lung Disease: Action As An Activator Or Potentiator Of Pulmonary Phagocytes

Recruitment and activation of phagocytic cells after inhalation of occupational dusts has been implicated in the development of pulmonary inflammation, fibrosis, or emphysema. Plateletactivating factor has been described recently as a potent inflammatory agent. The objective of the present study was to investigate if platelet-activating factor might play a role in the inflammatory response of the lung to occupational dusts. In vitro exposure of alveolar macrophages to cotton dust (4 mg/ml), silica (10 mg/ml), or coal dust (10 mg/ml) results in the release of picomole levels of platelet-activating factor with a potency of cotton dust > silica > coal dust. Time course studies indicate that platelet-activating factor release from alveolar macrophages is maximal approximately 10 minutes after in vitro exposure to silica. In vitro, platelet-activating factor is a direct stimulant of polymorphonuclear leukocytes increasing chemiluminescence 2.3 ± 0.3 fold above control. The maximal response occurs in the dose range of 10-10 to 10-7M platelet activating factor. In addition, plateletactivating factor potentiates the response of polymorphonuclear leukocytes to a second stimulant; i.e., chemiluminescence generated from polymorphonuclear leukocytes exposed to plateletactivating factor (10-9M) plus chemotactic peptide (FMLP, 10-9M) is 88 ± 22% greater than the sum of the separate effects of these stimulants. In contrast, platelet-activating factor is not a direct stimulant of alveolar macrophages in vitro, having no stimulatory effect on chemiluminescence or superoxide anion release even at levels of 10-6 to 10-5M platelet-activating factor. However, platelet-activating factor (10-5M) does potentiate zymosan-stimulated activation of chemiluminescence and superoxide release from alveolar macrophages by 117 ± 56% and 30 ± 4%, respectively. In conclusion, these data indicate that exposure of the lung to occupational dusts results in the release of platelet-activating factor which may activate polymorphonuclear leukocytes and potentiate the responsiveness of alveolar macrophages to dust. The net result would be pulmonary inflammation and hypersecretion of reactive species by pulmonary phagocytes which could lead to tissue damage and pulmonary disease.