부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.micinf.2006.10.009 Byline: Christine Comera (a)(b), Karine Andre (a), JoA'lle Laffitte (a), Xavier Collet (c), Pierre Galtier (a), Isabelle Maridonneau-Parini (b) Abbreviations: A. fumigatus, Aspergillus fumigatus; IPA, invasive pulmonary aspergillosis; MEM/HEPES, HEPES-buffered minimal essential medium; n-FMLP, n-formyl-Met-Leu-Phe; pCPT-cAMP, 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate; Rp-cAMP, adenosine 3',5'-cyclic monophosphothioate Rp-isomer triethylammonium salt; OZ, opsonized zymosan; Z, zymosan Abstract: Gliotoxin is a mycotoxin having a considerable number of immuno-suppressive actions and is produced by several moulds such as Aspergillus fumigatus. In this study, we investigated its toxic effects on human neutrophils at concentrations corresponding to those found in the blood of patients with invasive aspergillosis. Incubation of the cells for 10min with 30-100ng/ml of gliotoxin inhibited phagocytosis of either zymosan or serum-opsonized zymosan without affecting superoxide production or the exocytosis of specific and azurophil granules. Gliotoxin also induced a significant re-organization of the actin cytoskeleton which collapsed around the nucleus leading to cell shrinkage and the disappearance of filopodia. This gliotoxin-induced actin phenotype was reversed by the cAMP antagonist Rp-cAMP and mimicked by pCPT-cAMP indicating that it probably resulted from the deregulation of intracellular cAMP homeostasis as previously described for gliotoxin-induced apoptosis. By contrast, gliotoxin-induced inhibition of phagocytosis was not reversed by Rp-cAMP but by arachidonic acid, another member of a known signalling pathway affected by the toxin. This suggests that gliotoxin can affect circulating neutrophils and favour the dissemination of A. fumigatus by inhibiting phagocytosis and the consequent killing of conidia. Author Affiliation: (a) INRA UR 66 Laboratoire de Pharmacologie et Toxicologie, 180 chemin de Tournefeuille, 31931 Toulouse Cedex 9, France (b) Institut de Pharmacologie et de Biologie Structurale, UMR CNRS 5089, 205 Route de Narbonne, 31077 Toulouse Cedex, France (c) Institut Federatif de Recherche Claude de Preval, IFR 30, Centre de Physiopathologie de Toulouse-Purpan, Institut National de la Sante et de la Recherche Medicale, Unite 563, BAcentst C, Departement Lipoproteines et Mediateurs Lipidiques, HA[acute accent]pital Purpan, 31024 Toulouse cedex 3, France Article History: Received 21 July 2006; Accepted 11 October 2006