Suppression of Inhaled Particle Cytotoxicity by Pulmonary Surfactant and Re-toxification by Phospholipase: Distinguishing Properties of Quartz and Kaolin (bbbc09fd-1d76-41bd-b1b0-8470dd68e3ad)

"Abstract—Inhaled particle contact with pulmonary surfactant in the hypophase lining pulmonary alveoli was modelled in vitro by exposing two respirable sized dusts, kaolin and silica quartz, to lecithin, a major component of pulmonary surfactant, emulsified in physiological saline. Lecithin adsorbs to the dusts upon incubation at 3TC and suppresses their cytotoxicity as measured by pulmonary macrophage and erythrocyte assays, suggesting that pulmonary surfactant provides a defence system against prompt cell membrane lysis by inhaled dusts. Subsequent pulmonary macrophage phagocytosis and lysosomal enzyme digestion of the coated dusts was modelled in vitro by incubation with phospholipase A2 for one hour. With increasing lipase activity, silica haemolytic potential was restored to native silica levels. Kaolin was retoxified to levels far in excess of native kaolin haemolytic potential. Elution, thin layer chromatography and phosphate assay of treated dusts indicate that most lecithin on silica is digested to lysolecithin and desorbed, silica retoxification being due to surface and adherent lysolecithin effects. Most lecithin on kaolin is not digested in the same time; that which is. results in adherent lysolecithin which is responsible for the kaolin retoxification. Digestion with phospholipases A2 and C together produces only weakly retoxified kaolin. Results suggest that surface adsorption properties which control the adherence of prophylactic surfactant distinguish the pathogenic potentials of quartz, kaolin and mixed dust.INTRODUCTIONERYTHROCYTE HAEMOLYSIS and pulmonary macrophage enzyme release assays show quantitatively comparable high cytotoxicities for both silica quartz and kaolin respirable sized dusts (BROWN, et al., 1980; DANIEL and LE BOUFFANT, 1980.) This contrasts with the strong potential for respirable quartz dust to induce pulmonary fibrosis and the much more limited potential of kaolin dust to do the same (MORGAN and SEATON, 1975).In an attempt to understand this anomalous situation, assays were performed on quartz and kaolin dusts incubated with dipalmitoyl lecithin emulsified in physiological saline, to simulate the initial contact of a respired dust with the pulmonary alveolar hypophase. The ability of kaolin dust to adsorb dipalmitoyl lecithin from physiological saline has been quantified (WALLACE, et al., 1975). Such lecithin treatment suppresses the cytotoxicity of both silica and kaolin to background levels (WALLACE, et a1.,1984).Surfactant coated detoxified dusts should then be phagocytised by pulmonary macrophages, incorporated into a macrophage secondary lysosome and exposed to hydrolytic lysosomal enzymes. Among these is phospholipase A2, which hydrolyses diacyl lecithin to lysolecithin. This was modelled by incubating lecithin treated dusts with phospholipase A2 in vitro to determine if the enzyme can digest the dust-adsorbed lecithin, and if the retoxification differs between the two dusts in a manner which might distinguish their pathogenicity."