title: The effect of hexafluorocyclobutene on rat bronchoalveolar lavage fluid surfactant phospholipids and alveolar type II cells.
abstract: Hexafluorocyclobutene (HFCB), a reactive organohalogen gas, causes overwhelming pulmonary oedema. We investigated its effect on the rat lung surfactant system, comparing its action on type II pneumocytes with air-exposed rats. The inflammatory cell population and protein content of bronchoalveolar lavage fluid was analysed following exposure to air or HFCB (LCt30). Six rat lung phospholipids were measured by high-performance liquid chromatography, following solid phase extraction (SPE) from lavage fluid. Transmission electron microscopy (TEM) was used to visualise effects on alveolar type II cell ultrastructure. HFCB caused changes in cell populations and increased lavage fluid protein compared to controls, suggesting a permeability oedema. Changes in the total amount and percentage composition (sustained decrease in phosphatidylglycerol and phosphatidylcholine) of surfactant phospholipids also occurred. TEM observations indicated no direct ultrastructural damage to the type II cells, but showed initial, rapid release of surfactant into the alveolar space. HFCB altered the surfactant system in a manner similar to that shown following another reactive organohalogen gas, perfluoroisobutene (PFIB), but differently to that after phosgene. These differences suggest different mechanisms of action even though pulmonary oedema is the final injury for all gases. Better knowledge of the mechanisms involved will improve prospects for prophylactic/therapeutic intervention.
authors.affiliation: BioMedical Sciences Department, Chemical and Biological Defence Sector, Salisbury, Wiltshire, UK.
authors.forename: B
authors.initials: B
authors.lastname: Jugg
authors.forename: J
authors.initials: J
authors.lastname: Jenner
authors.forename: J N
authors.initials: JN
authors.lastname: Hughes
authors.forename: P
authors.initials: P
authors.lastname: Rice
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003503:Cyclobutanes / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D006845:Hydrocarbons, Fluorinated / Q000009:adverse effects* / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008854:Microscopy, Electron; D010743:Phospholipids / Q000032:analysis / Q000737:chemistry*; D011650:Pulmonary Alveoli / Q000737:chemistry / Q000473:pathology* / Q000648:ultrastructure; D011654:Pulmonary Edema / Q000139:chemically induced*; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000032:analysis / Q000737:chemistry*; D005466:Fluorocarbons
chemical_list: D003503:Cyclobutanes; D006845:Hydrocarbons, Fluorinated; D010743:Phospholipids; D013501:Surface-Active Agents; C092434:hexafluorocyclobutene; D005466:Fluorocarbons