Xenopus laevis Oocytes as a Model System for Studying the Interaction Between Asbestos Fibres and Cell Membranes.
The mode of interaction of asbestos fibres with cell membranes is still debatable. One reason is the lack of a suitable and convenient cellular model to investigate the causes of asbestos toxicity. We studied the interaction of asbestos fibres with Xenopus laevis oocytes, using electrophysiological and morphological methods. Oocytes are large single cells, with a limited ability to endocytose molecular ligands; we therefore considered these cells to be a good model for investigating the nature of asbestos/membrane interactions. Electrophysiological recordings were performed to compare the passive electrical membrane properties, and those induced by applying positive or negative voltage steps, in untreated oocytes and those exposed to asbestos fibre suspensions. Ultrastructural analysis visualized in detail, any morphological changes of the surface membrane caused by the fibre treatment. Our results demonstrate that Amosite and Crocidolite-type asbestos fibres significantly modify the properties of the membrane, starting soon after exposure. Cells were routinely depolarized, their input resistance decreased, and the slow outward currents evoked by step depolarizations were dramatically enhanced. Reducing the availability of surface iron contained in the structure of the fibres with cation chelators, abolished these effects. Ultrastructural analysis of the fibre-exposed oocytes showed no evidence of phagocytic events. Our results demonstrate that asbestos fibres modify the oocyte membrane, and we propose that these cells represent a viable model for studying the asbestos/cell membrane interaction. Our findings also open the possibly for finding specific competitors capable of hindering the asbestos-cell membrane interaction as a means of tackling the long-standing asbestos toxicity problem.
*Department of Life Sciences; Centre for Neuroscience B.R.A.I.N., University of Trieste, 34127 Trieste, Italy; and Department of Pharmacology, UCL School of Pharmacy, London, UK WC1N 1AX *Department of Life Sciences; Centre for Neuroscience B.R.A.I.N., University of Trieste, 34127 Trieste, Italy; and Department of Pharmacology, UCL School of Pharmacy, London, UK WC1N 1AX.
Annalisa
A
Bernareggi
*Department of Life Sciences; Centre for Neuroscience B.R.A.I.N., University of Trieste, 34127 Trieste, Italy; and Department of Pharmacology, UCL School of Pharmacy, London, UK WC1N 1AX *Department of Life Sciences; Centre for Neuroscience B.R.A.I.N., University of Trieste, 34127 Trieste, Italy; and Department of Pharmacology, UCL School of Pharmacy, London, UK WC1N 1AX.
Elisa
E
Ren
*Department of Life Sciences; Centre for Neuroscience B.R.A.I.N., University of Trieste, 34127 Trieste, Italy; and Department of Pharmacology, UCL School of Pharmacy, London, UK WC1N 1AX.
Violetta
V
Borelli
*Department of Life Sciences; Centre for Neuroscience B.R.A.I.N., University of Trieste, 34127 Trieste, Italy; and Department of Pharmacology, UCL School of Pharmacy, London, UK WC1N 1AX.
Francesca
F
Vita
*Department of Life Sciences; Centre for Neuroscience B.R.A.I.N., University of Trieste, 34127 Trieste, Italy; and Department of Pharmacology, UCL School of Pharmacy, London, UK WC1N 1AX.
Andrew
A
Constanti
*Department of Life Sciences; Centre for Neuroscience B.R.A.I.N., University of Trieste, 34127 Trieste, Italy; and Department of Pharmacology, UCL School of Pharmacy, London, UK WC1N 1AX zabucchi@units.it.
Giuliano
G
Zabucchi
D000818:Animals; D017639:Asbestos, Amosite / Q000633:toxicity*; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D002462:Cell Membrane / Q000187:drug effects* / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D005260:Female; D007501:Iron / Q000633:toxicity; D007502:Iron Chelating Agents / Q000494:pharmacology; D008564:Membrane Potentials; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D023421:Models, Animal; D009865:Oocytes / Q000187:drug effects* / Q000648:ultrastructure; D013997:Time Factors; D014982:Xenopus laevis
D007502:Iron Chelating Agents; D017638:Asbestos, Crocidolite; D017639:Asbestos, Amosite; D007501:Iron
Amosite; Crocidolite; Xenopus oocytes; asbestos fibres; electron microscopy; two-microelectrode voltage-clamp