Effects of phospholipid surfactant on apoptosis induction by respirable quartz and kaolin in NR8383 rat pulmonary macrophages.
Gao-N; Keane-MJ; Ong-T; Ye-J; Miller-WE; Wallace-WE
Toxicol Appl Pharmacol 2001 Sep; 175(3):217-225
Apoptosis was measured in rat alveolar macrophage NR8383 cells challenged in vitro with respirable quartz or kaolin dust and with the dusts pretreated with dipalmitoyl phosphatidylcholine (DPPC) to model conditioning of respired dusts by interaction with a primary phospholipid component of pulmonary surfactant. Quartz dust is known to induce apoptosis in vitro and in vivo. For this study, quartz and kaolin were compared as dusts of similar cytotoxicity in some in vitro assays but of differing pathogenic potential: quartz can cause significant pulmonary fibrosis while kaolin generally does not. NR8383 cells exposed to native quartz at concentrations from 50 to 400 microg/ml for 6 h showed a dose-dependent increase in apoptosis measured by the TdT-mediated dUTP-fluorescein nick end labeling (TUNEL), cell death ELISA, and DNA ladder formation assays, while native kaolin induced significant response only at the higher concentrations and only in the TUNEL and ELISA assays. For cell challenge from 6 h to 5 days at 100 microg/ml of dust, quartz was active at all times while kaolin was active only at 5 days. DPPC pre-treatment suppressed quartz activity until 3 days and kaolin activity through 5 days. Cellular release of lactate dehydrogenase, measured in parallel experiments to compare dust apoptotic and necrotic activities, indicated that components of serum as well as surfactant may affect kaolin in vitro expression of those activities.
DNA-damage; Dose-response; Drug-interaction; Silica-dusts; Fibrosis; Lung-cancer; Lung-fibrosis; Lung; Pneumoconiosis; Quartz-dust; Cytotoxicity; Respiratory-system-disorders; Pulmonary-system-disorders;
Author Keywords: apoptosis; cell death ELISA assay; dipalmitoylphosphatidylcholine; DNA ladder formation assay; kaolin; lactate dehydrogenase assay; pulmonary fibrosis; pulmonary surfactant; quartz; rat macrophage NR8383; respirable dust; serum; surfactant; TUNEL assay
National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, West Virginia, 26505
1332-58-7; 14808-60-7; 2644-64-6
Toxicology and Applied Pharmacology