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Human & Experimental Toxicology, Vol. 20, No. 5, 267-276 (2001)
DOI: 10.1191/096032701678227686

The efect of hexafluorocyclobutene on rat bronchoalveolar lavage fluid surfactant phospholipids and alveolar type II cells

B Jugg

J Jenner

J N Hughes

P Rice

BioMedical Sciences Department, Chemical and Biological Defence Sector, Porton Down, Salisbury, Wiltshire SP4 OJQ, UK

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 airexposed 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.

Key Words: pulmonary oedema • bronchoalveolar lavage • surfactant phospholipids • HPLC analysis • electron microscopy


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